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The last ancestor of all life

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Marc

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Aug 7, 2006, 8:39:27 AM8/7/06

The question about design or evolution of the bacterial flagellum
keeps coming up in Sean Pitman's replies to me so I thought I'd
look at the papers I've seen, but of course I started with a PubMed
search just to see what current results "flagellum evolution" gave.

Now, Sean refuses to accept any papers which use sequence
data comparisons so this message is not going to be of any
interest to him, but *Lurkers* and other interested readers of
talk.origins might consider looking at some of the most recent
papers that came up in my search results - Tom Cavalier-Smith
has two recent publications there, this one available for free...
suggesting the ancestor described in the subject line of this thread:

"Rooting the tree of life by transition analyses."
Biol Direct. 2006 Jul 11;1(1):19 [Epub ahead of print] PMID: 16834776
http://www.biology-direct.com/content/1/1/19
(for the abstract or the accepted paper in draft form, click the link)

and this one would be available to academics, students etc.:

"Cell evolution and Earth history: stasis and revolution."
Philos Trans R Soc Lond B Biol Sci. 2006 Jun 29;361(1470):969-1006.
PMID: 16754610

Abstract:
This synthesis has three main parts. The first discusses the
overall tree of life and nature of the last common ancestor
(cenancestor). I emphasize key steps in cellular evolution
important for ordering and timing the major evolutionary
innovations in the history of the biosphere, explaining especially
the origins of the eukaryote cell and of bacterial flagella and cell
envelope novelties. Second, I map the tree onto the fossil record
and discuss dates of key events and their biogeochemical impact.
Finally, I present a broad synthesis, discussing evidence for a
three-phase history of life. The first phase began perhaps ca 3.5
Gyr ago, when the origin of cells and anoxic photosynthesis
generated the arguably most primitive prokaryote phylum,
Chlorobacteria (= Chloroflexi), the first negibacteria with cells
bounded by two acyl ester phospholipid membranes. After this
'chlorobacterial age' of benthic anaerobic evolution protected
from UV radiation by mineral grains, two momentous quantum
evolutionary episodes of cellular innovation and microbial
radiation dramatically transformed the Earth's surface: the
glycobacterial revolution initiated an oxygenic 'age of cyanobacteria'
and, as the ozone layer grew, the rise of plankton; immensely
later, probably as recently as ca 0.9 Gyr ago, the neomuran
revolution ushered in the 'age of eukaryotes', Archaebacteria
(arguably the youngest bacterial phylum), and morphological
complexity. Diversification of glycobacteria ca 2.8 Gyr ago,
predominantly inhabiting stratified benthic mats, I suggest
caused serial depletion of 13C by ribulose 1,5-bis-phosphate
caboxylase/oxygenase (Rubisco) to yield ultralight late Archaean
organic carbon formerly attributed to methanogenesis plus
methanotrophy. The late origin of archaebacterial methanogenesis
ca 720 Myr ago perhaps triggered snowball Earth episodes by
slight global warming increasing weathering and reducing CO2
levels, to yield runaway cooling; the origin of anaerobic methane
oxidation ca 570 Myr ago reduced methane flux at source, stabilizing
Phanerozoic climates. I argue that the major cellular innovations
exhibit a pattern of quantum evolution followed by very rapid
radiation and then substantial stasis, as described by Simpson.
They yielded organisms that are a mosaic of extremely conservative
and radically novel features, as characterized by De Beer's phrase
'mosaic evolution'. Evolution is not evenly paced and there are
no real molecular clocks.

*****************************

Since this post is a result of looking into recent flagellum reports,
there is another paper worth a look, by Jekely and Arendt:

"Evolution of intraflagellar transport from coated vesicles and
autogenous origin of the eukaryotic cilium."
Bioessays. 2006 Feb;28(2):191-8. PMID: 16435301

Abstract:
The cilium/flagellum is a sensory-motile organelle ancestrally
present in eukaryotic cells. For assembly cilia universally rely
on intraflagellar transport (IFT), a specialised bidirectional
transport process mediated by the ancestral and conserved
IFT complex. Based on the homology of IFT complex proteins
to components of coat protein I (COPI) and clathrin-coated
vesicles, we propose that the non- vesicular, membrane-bound
IFT evolved as a specialised form of coated vesicle transport from
a protocoatomer complex. IFT thus shares common ancestry with
all protocoatomer derivatives, including all vesicle coats and the
nuclear pore complex (NPC). This has major implications for the
evolutionary origin of the cilium. First, it reinforces the tenet that
duplication and divergence of pre-existing structures, rather than
symbiosis, were the major themes during cilium evolution.
Second, it suggests that the initial step in the autogenous origin
of the cilium was the establishment of a membrane patch with
transmembrane proteins transported by the ancestral vesicle-coating
IFT complex. We propose a scenario for how the initial membrane
patch gradually protruded to enhance exposure to the environment,
then started to move, and finally compartmentalised to render
receptor signalling and ciliary beating more efficient.

**********************

So, perhaps I'll get on with the flagellum papers I was going to look
at in another thread or down this thread somewhere, but for now
these papers have caught my attention. (Think of them as "bed time
stories", Sean, bed time for "design" compared with evolution, that
is.)

Oh...
Sean - if you have trouble getting any of these (even the free one),
just go ahead and ask. I'm happy to help.

(signed) marc

Seanpit

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Aug 8, 2006, 4:51:32 PM8/8/06

Marc wrote:
> The question about design or evolution of the bacterial flagellum
> keeps coming up in Sean Pitman's replies to me so I thought I'd
> look at the papers I've seen, but of course I started with a PubMed
> search just to see what current results "flagellum evolution" gave.

When it comes to the topic at hand, not too many essays are better than
Matzke's. I'm sure you and the lurkers would be interested in reading
it. I discuss it and several other interesting papers dealing with
various aspects of flagellar evolution in fair detail on my website at:

http://www.detectingdesign.com/flagellum.html

Sean Pitman
www.DetectingDesign.com

nickm...@gmail.com

unread,

Aug 9, 2006, 7:21:37 PM8/9/06

This is an interesting (free!) paper, although broad brush as
Cavalier-Smith is mostly interested in the very big picture of
bacterial phylogeny.

This is about the evolutionary origin of the eukaryotic
cilium/flagellum, not the bacterial flagellum. But it is useful and
provides a puzzle piece about what role the Intraflagellar Transport
(IFT) complexes currently play, and might have played in the past.

IIRC Behe disses this paper in the Afterword to the 2006 edition of
Darwin's Black Box. However, we won't be able to get a really detailed
evolution model until we actually understand in detail the structure
and assembly of the mitotic spindle and the centriole, which we are a
long ways from doing. More here:
http://www2.ncseweb.org/kvd/exhibits/immune/immune_evo_bib_long.html

See "The Implications".

nickm...@gmail.com

unread,

Aug 9, 2006, 7:27:32 PM8/9/06

Seanpit wrote:
> Marc wrote:
> > The question about design or evolution of the bacterial flagellum
> > keeps coming up in Sean Pitman's replies to me so I thought I'd
> > look at the papers I've seen, but of course I started with a PubMed
> > search just to see what current results "flagellum evolution" gave.
>
> When it comes to the topic at hand, not too many essays are better than
> Matzke's. I'm sure you and the lurkers would be interested in reading
> it. I discuss it and several other interesting papers dealing with
> various aspects of flagellar evolution in fair detail on my website at:
>
> http://www.detectingdesign.com/flagellum.html
>
> Sean Pitman
> www.DetectingDesign.com

===============================
On top of this, what about the argument that similarities between
proteins of the F1F0-ATP synthetase and the flagellar type III export
apparatus support the notion that they share a common early ancestor?
In the very same breath Matzke adds, "Individually, the cited
similarities are easily attributable to chance, but together they are
at least suggestive."1 This sounds to me like some rather large gaps
are at least potentially present in the proposed pathway already.
===============================

LOL...

Nic

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Aug 9, 2006, 9:32:15 PM8/9/06

nickm...@gmail.com wrote:
<snip>

>
> This is about the evolutionary origin of the eukaryotic
> cilium/flagellum, not the bacterial flagellum. But it is useful and
> provides a puzzle piece about what role the Intraflagellar Transport
> (IFT) complexes currently play, and might have played in the past.
>
> IIRC Behe disses this paper in the Afterword to the 2006 edition of
> Darwin's Black Box. However, we won't be able to get a really detailed
> evolution model until we actually understand in detail the structure
> and assembly of the mitotic spindle and the centriole, which we are a
> long ways from doing. More here:

It's long been an impression of mine that the eukaryotic
cilium/flagellum is an organelle requiring another instance as its
predecessor. I.e. it it can't be rustled up from scratch by suitable
nuclear genes. Perhaps I think that because micrographs of cells
lacking cilia/flagella often show a centriole, which looks like a cross
section through one. Circumstantial, I know.

> http://www2.ncseweb.org/kvd/exhibits/immune/immune_evo_bib_long.html
>
> See "The Implications".
>

<snip>

'Rev Dr' Lenny Flank

unread,

Aug 9, 2006, 10:56:37 PM8/9/06

And, um, who the hell are you, again . . . . ?

================================================
Lenny Flank
"There are no loose threads in the web of life"

Creation "Science" Debunked:
http://www.geocities.com/lflank
DebunkCreation email list:
http://groups.yahoo.com/group/DebunkCreation/

Marc

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Aug 10, 2006, 10:18:30 AM8/10/06

...... snp

The topic at hand is you agreeing that your reply in the
other thread was based on an understanding of an immune
response in a given individual and misunderstood the very
nature of the immune system in evolution.

The fact that you can organise a lot of technical terms on a
web page about the flagellum does not mean in the slightest
that you understand what others are writing about it's evolution.

Since you are greatly mistaken about immune evolution, it would
only be natural that you are also mistaken about the little bit
sticikng out from some types of bacteria. As I said elsewhere,
I'll come back to you with some discussion of the flagellum later.

For the moment, I'm interested in what your arguments are as
far as the immune system showing any aspect of "design" or
if you agree with my understanding that evolution of the key
features of vertebrate adaptive immunity is understandable.

(signed) marc

Seanpit

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Aug 10, 2006, 4:46:02 PM8/10/06

The following is a repost from elsewhere dealing with similar comments
from Marc:

__________________

Marc wrote:
> Seanpit wrote:
> > Marc wrote:
> > > Seanpit wrote:
> > > > Marc wrote:
>
> ........... snip
>
> > > Note that I find your "high complexity" idea completely bogus since
> > > evolution seems to have done quite well without forcing new features
> > > to appear in the way you describe.
> >
> > I'm not describing how evolution works any different than you guys. The
> > evolution of a function like the flagellar motility system would have
> > to have created such a system via a series of relatively small
> > mutations over time - with each step being beneficially functional and
> > selectable. I'm not suggesting that evolution forces new features to
> > appear in any sort of unusual way. I'm suggesting that new functional
> > features simply didn't appear in the manner that *you* suggest they
> > appeared.
>
> I'm suggesting they appeared by evolution.

Of course you are. And, I'm describing how evolution is supposed to
work just like you guys. The problem is, the driving forces of
evolution, i.e., random mutation and natural selection, just can't
create systems of function that require a minimum of more than a few
thousand fairly specified bases of DNA.

> What are you suggesting? God, right? Or something like that?

I'm suggesting a highly intelligent agent of some kind was most
certainly involved in the creation of all systems of function in living
things that require a minimum of more than a few thousand fairly
specified bases of DNA.

> > >Take the immune system as an
> > > example. If we had to evolve a new antibody every time a pathogen
> > > evolved - evolving an antibody from scratch as a "high complexity
> > > novel feature" to survive past that next pathogen - each such step
> > > would have taken hundreds of thousands of years for such a novel
> > > function to be obtained. Obviously, that wouldn't work very well.
> >
> > The evolution of antibody specificity to different or changing antigens
> > is not high-level evolution. It is based on template matching where
> > each small improvement in the antibody-antigen match is preferentially
> > selected for by the immune system. Such improvements can be realized
> > in very short order because of this template-based system.
>
> Sean, I said "take the immune system as an example". I *did not*
> say "take an immune response as an example".

That's certainly how it sounded to me. You started talking about
changes in the pathogen, antigen changes, and the need for an immune
system that can compensate for these changes. Of course an entirely
new system doesn't need to evolve to detect such antigen changes! If
you are talking about the evolution of the immune system, then no, I
don't believe that the immune system evolved from ancestor creatures
that didn't have an immune system. The minimum coding requirement for
a useful immune system is far too complex for evolutionary mechanisms
to achieve even in trillions upon trillions of years of time.

> Don't you, trained
> as a doctor, know the difference between "Immune Response" and
> "Immune System"? You seem not to.

Oh, give me a break! It seemed to me you were talking about immune
response evolution. If you weren't, then you really have no
demonstrable back up for your stories of immune system evolution.
Again, you are left with exactly the same thing you are left with in
your other stories about how evolution must have happened - based
solely on sequence homologies.

< snip >

> > > Evolution happens to agree with you and does not even try to
> > > evolve such novel features in a one-by-one "high complexity"
> > > fashion,
> >
> > I never said the mechanism or the "fashion" had to be "highly complex".
> > I never said that at all. What I said was that the resulting
> > functional system had to require a minimum of more than a few thousand
> > fairly specified bases of DNA. There's a big difference here you know.
> > It is the result, not the mechanism to achieve the result, that needs
> > to go beyond very low levels of functional complexity.
>
> Duplicated gene regions, duplicated genomes and plain old
> duplicated genes - all sound bigger than "a few thousand" to me.

Duplicate genes or duplicate regions of a genome may indeed be many
thousands or tens of thousands or even millions of bases in size. Yet,
no new function is realized via a simple duplication of what was
already there. The only thing duplication does is make two out of one.
We are talking about new functions here Marc - not more of the same
thing. Do any novel functions arise, via gene duplication or any other
type of genetic change, that require more than a few thousand fairly
specified bases at minimum in order to work?

You do understand the difference here? - right? Do you understand that
there's a difference between making more of the same thing and creating
a new function?

> You have to get over this "complexity" thing, whatever that is.

This "complexity" thing is the basis of this entire discussion Marc.
You have to start to understand the relevance of functional complexity
to the problem of random mutations and natural selection working to
find more beneficial functions at higher and higher levels of
functional complexity.

If you don't even understand the topic, how can you think to be
presenting a reasonable rebuttal?

> > > opting instead for the immune recognition molecules
> > > (the kappa, lambda and gamma antibody chains and the alpha,
> > > beta, gamma and delta T-cell receptor chains) to generate an
> > > enormous range of binding pockets by bringing gene segments
> > > together - with "variable", "diversity", and "joining" segments
> > > between the constant and variable segments - and including a
> > > bit of random nucleotide insertion in the process to generate
> > > immune repertoires that can bind to epitopes on pathogens, to
> > > bind self epitopes (the price we pay is autoimmune disease here),
> > > and even to bind to targets that the pathogens have yet to evolve.
> >
> > Exactly - this is what I call template-matching evolution. The immune
> > system can fine-tune itself to recognize a host of never before
> > encountered non-self antigens. It does this by random mutation and
> > natural selection - sure enough. However, the antigen acts as a
> > template. The cells that produce the antibodies that match a given
> > foreign antigen the best are preferentially selected for reproduction.
> > Various mutations are introduced into the offspring of these parent
> > cells so that a narrower range of antibodies are produced. Those that
> > match the antigen the best are again selected for preferential
> > reproduction. The end result is a fine-tuned match, which did in fact
> > evolve rather quickly over time.
>
> Your understanding here is not about the genetics of the immune
> system, but about the changes in some antibodies (by somatic
> hypermutation) during the course of an immune response. That
> is *not* evolution (although an immune response does evolve as
> it goes through these events and others, such as switching the
> class of the heavy chain of the antibody).

Actually, this is evolution. It is a stepwise improvement in function
via random mutation and function-based selection.

> The binding site of an
> antibody has *nothing* to do with evolution - it is distinct and exempt
> from evolution because the changes to an antibody (even the nature
> of the antibody in the first place) do nothing to the genome in the
> reproductive cells.

Just because the gametes are not affected does not mean that directed
changes in immune system specificity isn't an example of evolution in
action. The generations that are important here are generations of
antibody producing cells. These generations do indeed change from one
generation to the next. Just because this information is not given to
the gametes of a given person, does not mean that evolution isn't
happening within that person's body.

> The fact that you may use a certain antibody does
> not mean your children or grandchildren will use the same antibody.
> Changes to the genome in an antibody-producing cell do not connect
> back to the reproductive cells and are not passed on by heredity.

This doesn't mean evolution isn't happening within a given immune
system - even if that information isn't passed on to children and
grandchildren. The evolution taking place here is between generations
of immune system cells.

> Antibody molecules are not passed down in evolution, only the
> system that generated them in the first place and the whole
> V-D-J recombination has to start all over again to produce brand
> new antibody binding sites in the next generation, every time.

That's true, but evolution is still happening within a given person's
immune system over time. Just because this evolution has to start over
in that person's offspring doesn't mean that evolution, real evolution,
isn't happening. It is.

> (Same for the TcR, but hypermutation isn't a feature there as
> it would undo the process of thymic education.)

Correct . . .

< snip >

> > > Did your designer create lupus? MS?
> > > RA? Type 1 diabetes? Or did evolution result in those conditions?
> >
> > Evolution does work on certain levels - to include the production of
> > various degenerative diseases such as various cancers and other
> > immune-based diseases such as the ones you mention here. None of these
> > are out of reach of evolutionary mechanisms. What is out of reach are
> > beneficial systems of function that require more than a few thousand
> > fairly specified bases of DNA - which cannot be build via template
> > matching evolution.
>
> Built...? Perhaps they can be built by duplication and mutation.
> Failure to read the literature will keep you misunderstanding this.

I have read the literature. None of what I have read discusses the
observed evolution of a novel function that requires a minimum of more
than a few thousand fairly specified bp of DNA. Sure, like you, lots
of papers suggested to me that do nothing more than tell stories about
how evolution must have happened based only on sequence homologies.

> > The overall systems of immunity were designed. These do not evolve.
> > The specificity of an immune system does evolve - as per design.
>
> This is the same sticky wicket that Behe got struck out on (to mix
> my metaphors). He *thought* the immune system was designed
> but he neglected to read the literature - the same mistake you are
> making, I suspect. There are lots and lots of papers that you haven't
> read on this topic and while I can point them out to you (and I will),
> it isn't up to me to read them for you. That's your job, if you want to
> know what is known about immune evolution. Certainly there isn't
> any "design" to it, I'm afraid, but we'll get to that. This is however
> the major point at which you are in error - thinking that the overall
> immune system is designed in some way or another.

Yes, this is the point of our discussion. You say that the various
immune systems, as a whole, evolved. I say that they were designed.
You say there are lots of papers talking about immune system evolution
- and I agree. There are a whole lot of papers giving one story after
another about how immune systems supposedly evolved. None of these are
based on observation of actual functional evolution of an immune system
of any kind. All of them are based on the supposed evolutionary
relationship between sequence homologies.

> Let's look at it this way, was it part of the immate system that
> was designed, part of the adaptive system, all of both systems
> or just part of both systems?

All of both systems were designed to work like they do. . . cellular
and humoral.

> What about the pathogens?

What about pathogens? If a functional system within a pathogen
requires more than a few thousand bp of DNA, at minimum, then yes, it
too was designed.

> It is
> the song and dance of evolution that pathogens and immune
> systems evolve with respect to each other.

That is the song and dance of the ToE. Unfortunately, it is a fairly
tale.

> Where does the design fit in?

Design fits in at the point where more than a few thousand fairly
specified based of DNA are required.

> (I say that it doesn not fit in at all and it is up to
> you to explain where I'm wrong about saying this, I'm afraid.)

That's true. It is up to me and I have been explaining it too you. It
is just that you are blind to the obvious so far . . . I'm afraid. You
can only lead a horse to water . . .

> Let's look at your comment about the immune system and design -
> "overall systems of immunity were designed. These do not evolve."
>
> Explain to me then why various vertebrates differ in the nature of
> their immune systems (in a way that fits with evolution)?
> Examples: the chicken and it's minimal MHC; birth and death
> of primate MHC genes; linkage of the class I and II MHC regions
> apart from the bony fish and what about the evolution of the
> site-specific recombination that drives the generation of T-cell
> receptors and antibody binding sites in the first place?

Different types of creatures benefit from different types of immune
systems? The argument that no intelligent designer would have done it
that way just doesn't fly with me. In fact, until you can do better
yourself, I'd say it is more arrogant than a six-year-old kid telling
an famous architect that he/she didn't build his/her skyscraper
correctly.

> Then you said "The specificity of an immune system does evolve - as
> per design." which *completely misunderstands "evolution" as a term.

I disagree. I think you misunderstand the term "evolution" here.

> Sure, there is an evolution of an immune response, but that is not
> going to impact on an organism's heredity ( where the "Big E"
> type evolution happens).

It doesn't have to impact on heredity in order to meet criteria for
"evolution" - i.e., improved functional change over time via random
mutation and natural selection.

< snip >

> > > What if I suggest without even reading them that
> > > all they are are "just so stories"? That's what you are doing, dude.
> >
> > Do you have a paper that isn't describing what supposedly happened? -
> > that even purports to describe an actual observation of evolution
> > actually happening? - in a way that produces a beneficial function that
> > requires more than a few thousand fairly specified bases? Dude?
>
> "Dude" me all you like, but such an observation is a bogus request.
>
> You somehow feel this is important in that it would thereby disprove
> your designer, but you have no way in which the lack of such an
> observation *proves* your designer, do you? I say the point is moot.

You don't understand how science works. You never "prove" anything in
science. The scientific method is only useful in that one is capable
of disproving theories. No theory is ever fully proven by science. In
fact, it is because of the impossibility of proving anything that
science is actually useful. If anything ever became an "absolute
truth", science would no longer be needed. The usefulness of
"predictive power" is based in the non-absolute nature of the
prediction.

I'm very surprised that, as a published scientist, you are apparently
unaware of how science works.

> You cannot give me any example of something that might be a
> product of design (apart from a flagellum) - why is that? Think a bit.

I can give you lots of examples. Both DNA transcription and RNA
translation require far more functional complexity than does a
flagellar motility system. Various cellular functions, like pinocytosis
or phagocytosis are also highly complex. Useful photon detection
(i.e., the most rudimentary vision system) is very highly complex. And
on and on . . . Every single living thing requires very highly complex
functional systems in order to exist.

> I do not see where you have addressed human speech - hopefully
> that means you are going to read the papers before you comment.

I don't see where you have shown that the code for basic human speech
has been observed to evolve. Where are your published observations of
this ability? - beyond sequence or structural homology comparisons?

< snip >

> > This is where your just-so stories come into play. This notion of
> > yours that "higher-function" occurs "sometimes" via such means has
> > never been demonstrated - ever. There is not one single example.
>
> I am not saying that higher order features appear at all - you are.

I'm not saying that higher order functions must appear all at once
either. Just show one step evolving within the supposed pathway of a
higher-level function - like flagellar motility.

> It would not surprise me at all if such features *never* appeared,
> but that doesn't mean that *design* must appear instead, does it?

Not at all. Design doesn't have to do anything. It is just that if a
high-level function does appear, it most certainly did appear via the
help of design - not random mutation and natural selection.

> You have ignored the paper on protein evolution I have suggested
> again - the offer to send it to you still stands. Hell - give me a few
> weeks and I'll put about a thousand papers onto a CD and I'll post
> the whole bunch to you if you like. (Wait... they are all just stories
> and you aren't interested, right?)

That's right. I'm not interested in thousands of papers discussing
sequence homologies. I've already read many of these types of papers.
They simply are missing/not discussing the obvious problem - the
non-beneficial gap problem.

> > List
> > an actual quote from one of your litany of references that actually
> > claims to demonstrate such a thing beyond the appeal to sequence
> > homologies. If you are able to do this, I'll read the paper you
> > reference. Otherwise, why should I waist my time on dozens of
> > irrelevant articles and papers? You love to list off many references.
> > You are very loath to actually quote anything from any of them.
>
> I'm happy to, but you are better served by reading them yourself.

I will read them if your quote is actually relevant to the topic - if
it actually appears to counter any of my main points. If you come up
with such a paper, I'll be most interested in reading it for myself.
Until then, neither your or the papers you have presented say anything
about the points I'm actually presenting here.

> > So
> > far, I have very little confidence that your understanding of the main
> > issue here lends itself to presenting a paper that is actually
> > relevant.
>
> The main issue is that your idea about "functional complexity"
> is unnecessary. It is wrong. It doesn't even exist. It doesn't happen.

You are quite mistaken. All functional protein-based systems require a
minimum number of amino acid residues as well as a minimum degree of
specific arrangement/association of these residues relative to each
other. These minimum requirements are very real. Every single type of
function has its own minimum requirements. Some systems have greater
minimum requirements than do others. Some systems have very few
minimum requirements. Others have very large minimum requirements.
Very simple systems can and do evolve - and quickly. Those systems
that have somewhat greater minimum requirements take longer to evolve,
or do not do so nearly as readily. Those systems that have even
moderate minimum requirements, that go beyond just a few hundred fairly
specified residues, never evolve.

> You only ever cite the flagellum, and that is just normal evolution
> and not some designer-built guided evolution. It's not. But that is
> for another thread, since those papers are ones I haven't read in
> a while (and they aren't even on this PC, I think).

Good luck . . .

> Go read the Annual Review - Biochemistry paper. Please. And
> think a bit about what I am telling you about immunity before
> you reply next time - you were quite off base in this reply.

Ditto . . . about the "off base" part.

> (signed) marc

Sean Pitman
www.DetectingDesign.com

Frank J

unread,

Aug 10, 2006, 8:04:43 PM8/10/06

Marc wrote:
(snip)

> The topic at hand is you agreeing that your reply in the
> other thread was based on an understanding of an immune
> response in a given individual and misunderstood the very
> nature of the immune system in evolution.
>
> The fact that you can organise a lot of technical terms on a
> web page about the flagellum does not mean in the slightest
> that you understand what others are writing about it's evolution.

Nor does it rule out the posibility that he understands it but
misrepresents it anyway.

(snip)

Marc

unread,

Aug 10, 2006, 9:24:43 PM8/10/06

****Top-post Alert****

Top-posted comment made by Sean - see note below:

Seanpit wrote:
> The following is a repost from elsewhere dealing with similar comments
> from Marc:
>
> __________________
>
>
> Marc wrote:
> > Seanpit wrote:

> > ........... snip
> >
> > > > Note that I find your "high complexity" idea completely bogus since
> > > > evolution seems to have done quite well without forcing new features
> > > > to appear in the way you describe.
> > >
> > > I'm not describing how evolution works any different than you guys.

... small snp....

Here is the thing, Sean - you insist that *something* must be making
bits of new genetic material beyond a certain size of fragment that you
think is an upper limit, and you insist that gene duplication can only
make something that is already there and so there *must* be a designer
working to make those bigger things, right? So what if you are just a
little bit wrong about the outcome of gene duplication? What if, as is
now accepted in science, duplication and divergence is a major force
in the development of new functions? It sort of weakens the need for
your "designer", right?

This post is a copy of your reply to me in a different thread, right?
You have a statement top-posted above that would be slightly
different from the other reply (i.e. it is lacking), but the fact that
you have copied your entire reply here from another thread (instead
of just answering my question with an original reply) is analogous
to a genetic duplication event. Nice one, Sean! Already my reply
in this thread is different to the comments that I will be making to
the original version of this message in the other thread. Here, I am
considering how this very message serves as an illustration of how
divergence of duplicated material works, while back in the original
message I will most likely reply about how you should go back and
read my comments on the basis of the immune system a bit more
carefully since I still think you fail to grasp them. (Of course, not
making a reply to that thread is also a quite valid example of how
evolution functions with respect to duplicated material. If the gene
has a quite essential role, then one of the copies needs to maintain
that function.)

> Of course you are. And, I'm describing how evolution is supposed to
> work just like you guys. The problem is, the driving forces of
> evolution, i.e., random mutation and natural selection, just can't
> create systems of function that require a minimum of more than a few
> thousand fairly specified bases of DNA.

You again overlook the other driving force in evolution, gene
duplication,
that answers your conundrum quite clearly. Perhaps you might want to
read the Annual Review Biochem. paper I cited (which you don't seem
to have looked at yet), or the paper that John pointed out recently:
"Allelic divergence precedes and promotes gene duplication"
Evolution Int J Org Evolution. 2006 May;60(5):881-92. PMID: 16817530

Try these as well:
"Protein family expansions and biological complexity"
PLoS Comput Biol. 2006 May;2(5):e48. Epub 2006 May 26.
PMID: 16733546
http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=16733546

"Widespread genome duplications throughout the history of
flowering plants" Genome Res. 2006 Jun;16(6):738-49.
PMID: 16702410

"Gene duplication and functional divergence of the zebrafish
insulin-like growth factor 1 receptors."
FASEB J. 2006 Jun;20(8):1230-2. Epub 2006 May 16.
PMID: 16705083

"Combinatorial RNA interference in C. elegans reveals that
redundancy between gene duplicates can be maintained for
more than 80 million years of evolution."
Genome Biol. 2006 Aug 2;7(8):R69 [Epub ahead of print]
PMID: 16884526

"Frequent appearance of novel protein-coding sequences
by frameshift translation"
Genomics. 2006 Aug 3; [Epub ahead of print]
PMID: 16890400

(This last report seems quite interesting - I'd like to hear
your thoughts about this one after you read it, Sean.)

..... another small snp .....

> >
> > Sean, I said "take the immune system as an example". I *did not*
> > say "take an immune response as an example".
>
> That's certainly how it sounded to me.

Read those passages again, Sean. Take your time.

I'll try to expand on some of it later, with citations for you
to ignore or claim you have already looked at, and I will
even try to point out the passage of importance as you
have requested, just to try and get you past your barrier
of misunderstanding you are caught behind. (In the other
thread - just to show independent evolution of the duplicated
message you have provided for this example.)

>You started talking about
> changes in the pathogen, antigen changes, and the need for an immune
> system that can compensate for these changes.

Not exactly. The immune response in an individual is more or less
completely unique, even in twins I would dare say, and it is this
evolutionary system, going back some 450 million years, that used
this right from the start - it's one of the very reasons that
vertebrates
were able to evolve so well, by a system of self-recognition and the
ability to respond to non-self and altered-self which evolved alongside
the established innate immune system. Each individual has their
strengths and weaknesses in their immune repertoires, but that is
*NOT EVOLUTION*, it is the result of a system that did evolve but
the immune response in an individual does *NOT* itself contribute
to downstream evolution (except in the general sense that some
components like an given MHC allele or variation in a cytokine or
receptor can be selected for or against) since the antibody binding
sites and the TcR binding sites are *NOT* in the germline.

> Of course an entirely
> new system doesn't need to evolve to detect such antigen changes! If
> you are talking about the evolution of the immune system, then no, I
> don't believe that the immune system evolved from ancestor creatures
> that didn't have an immune system. The minimum coding requirement for
> a useful immune system is far too complex for evolutionary mechanisms
> to achieve even in trillions upon trillions of years of time.

Oh, Sean - quit the "trillions of years" stuff. Using such excess of
scale is trite and shows no appreciation for deep time. A thousand
million years is an extraordinary long time and there is no need to
make it sound otherwise. My six year old has a better respect for the
scale of numbers than that. (He is actually *very* good with numbers,
perhaps partly from the number of x-box game scores that go up
into millions and such that he has seen and can grasp quite well.)
Your use of "trillions" is stupid.

......... snp the rest here .....
(This now becomes a protein domain doing an exon shuffle in the
duplicated-message/thread model of gene duplication in evolution)

(signed) marc

Robert Maas, see http://tinyurl.com/uh3t

unread,

Aug 10, 2006, 9:36:42 PM8/10/06

> From: "Seanpit" <seanpitnos...@naturalselection.0catch.com>

> The problem is, the driving forces of evolution, i.e., random
> mutation and natural selection, just can't create systems of function
> that require a minimum of more than a few thousand fairly specified
> bases of DNA.

Why couldn't such a multi-thousand-base sequence for this "new"
function have evolved from some other sequence of comparable length
that coded some "old" function, requiring only five or ten changes from
the old sequence to the new sequence?

> Of course an entirely new system doesn't need to evolve to detect
> such antigen changes! If you are talking about the evolution of the
> immune system, then no, I don't believe that the immune system evolved
> from ancestor creatures that didn't have an immune system.

You seem to be claiming that the immune system itself was a *new*
system unrelated to anything that existed before. On what basis do you
make such a claim?

> The minimum coding requirement for a useful immune system is far too
> complex for evolutionary mechanisms to achieve even in trillions upon
> trillions of years of time.

Let's do some arithmetic. Suppose about once every million years
there's a burst of adaption, whereby ten DNA bases are changed,
resulting in a new function different from before. So over the course
of a billion years, one thousand of these bursts would accumulate,
totalling ten thousand DNA-base changes, i.e. virtually every DNA base
(in the multi-thousand sequence which now codes for the immune system)
would be different now from a billion years ago. That doesn't match
your claim that trillions of years would be required.

> Duplicate genes or duplicate regions of a genome may indeed be many
> thousands or tens of thousands or even millions of bases in size. Yet,
> no new function is realized via a simple duplication of what was
> already there. The only thing duplication does is make two out of one.

Correct so-far. But then one of the copies begins mutating toward new
functions, no longer required to do the old function because the other
copy can do it just fine.

> We are talking about new functions here Marc - not more of the same
> thing.

There's no such thing as *new* functions. Every function is a small
change (in DNA sequence) from some earlier function. Did you see the
report about five point mutations that changed some protein such that
before those five changes it was virtually useless at making the
bacterium resistant to a particular antibiotic whereas after those five
changes the resultant bacterium was very resistant to the antibiotic?
(There was a numeric scale of resistance, which was only 0.05 at the
start and 5000 after the five changes, approximately.)

> Do any novel functions arise, via gene duplication or any other
> type of genetic change, that require more than a few thousand fairly
> specified bases at minimum in order to work?

Sure, if there was some *other* function already existing, whereby only
five or ten changes were needed to make the new function work.

> Do you understand that there's a difference between making more of
> the same thing and creating a new function?

Duplication makes extra copy of DNA for old function, then a few
mutations changes it to a "new" function. Nothing is really new, just a
variation on what came before.

> You have to start to understand the relevance of functional
> complexity to the problem of random mutations and natural selection
> working to find more beneficial functions at higher and higher levels
> of functional complexity.

You may be arguing the wrong end of this! At high levels of complexity,
there are so many interreactions between the various components that a
point mutation in one gene can cause a protein to take on a very
different shape that interreacts with other parts in a totally
different way, such that a single point mutation creates what looks
like a totally novel function. Mutations are random, and most of these
new functions are worthless or harmful so they are lost. But every so
often a mutation chances upon a beneficial novel function. In the
entire biosphere, the number of such random mutations per year is
immense, and it doesn't take more than one beneficial novel function
per million mutations to yield significant progress.

> There are a whole lot of papers giving one story after another about
> how immune systems supposedly evolved. None of these are based on
> observation of actual functional evolution of an immune system of any
> kind. All of them are based on the supposed evolutionary relationship
> between sequence homologies.

Are you saying that people have read out the sequence of various
homologous genes, and generated minimum-evolution trees to connect all
these sequences together, and thereby inferred the various evolutionary
paths from a common-ancestral gene to all those current-day genes?
That sounds fine to me. What's your problem with that methodology?

> ... if a high-level function does appear, it most certainly did

> appear via the help of design - not random mutation and natural
> selection.

That's a rather arrogant statement for you to make, given that you
haven't explored all possible evolutionary paths to be sure none of
them achieve the high-level function.

> I'm not interested in thousands of papers discussing sequence
> homologies. I've already read many of these types of papers. They
> simply are missing/not discussing the obvious problem - the
> non-beneficial gap problem.

Given an evolutionary tree inferred from a collection of homologous
genes, given a single branch within that tree, have you actually
computed the phenotypes generated by all possible sequences of single
mutations that span that branch, and verified that not a single such
sequence of mutations could have been driven by increased benefit all
along the sequence?

> All functional protein-based systems require a minimum number of
> amino acid residues as well as a minimum degree of specific
> arrangement/association of these residues relative to each other.

Not really. Make a few changes and the protein now works differently,
which might have been useful in the past. The requirement for the
particular arrangement of residues is only if you insist on exactly the
same function. But how can you insist that same exact function was
always needed in the past? You don't know what pressure the environment
placed on ancestors, and what variant proteins might have been useful
back then.

> Those systems that have even moderate minimum requirements, that go
> beyond just a few hundred fairly specified residues, never evolve.

Only if you insist that ancestors required exactly the same function.

'Rev Dr' Lenny Flank

unread,

Aug 10, 2006, 11:17:43 PM8/10/06

Seanpit wrote:
>
<snip>

>
> I'm suggesting a highly intelligent agent of some kind was most
> certainly involved in the creation of all systems of function in living
> things that require a minimum of more than a few thousand fairly
> specified bases of DNA.

<snip>

And what it is, again, that you think God -- uh, I mean "a highly
intelligent agent of some kind" -- did, exactly, to produce them?

What mechanisms did He --- uh, I mean "it" -- use to do whatever the
heck you think He -- uh, I man "it" -- did?

Where, again, can we see Him -- uh, I mean "it" -- using these
mechanisms today to do . . . well . . . anything?

Or is "God -- uh, I mean 'a highly intelligent agent of some kind' --
diddit !!!!!" the extent of your, uh, "design theory" . . . . . ?

(sigh) No WONDER nobody takes IDers seriously.

Marc

unread,

Aug 11, 2006, 12:44:50 AM8/11/06

Sean, note that the citations I made in my earlier reply in this
thread (that first paper is *very* interesting, too!) were for articles
that came out in the last week or so. Please read these reports
a.s.a.p. so that next week I can point you to whatever the
forthcoming few papers are that come out on this topic then.

I'm fairly sure that the next few papers to turn up in a PubMed
search on "duplication divergence" or "gene family" or whatever
will just add to the support of duplication as a mechanism and
there will almost certainly be no papers published next week
that will take away from it. Do you perhaps sense a trend here?

(signed) marc

Von R. Smith

unread,

Aug 11, 2006, 3:26:58 PM8/11/06

Seanpit wrote:
> The following is a repost from elsewhere dealing with similar comments
> from Marc:
>
> __________________
>
>
> Marc wrote:
> > Seanpit wrote:
> > > Marc wrote:
> > > > Seanpit wrote:
> > > > > Marc wrote:
> >
> > ........... snip
> >
> > > > Note that I find your "high complexity" idea completely bogus since
> > > > evolution seems to have done quite well without forcing new features
> > > > to appear in the way you describe.
> > >
> > > I'm not describing how evolution works any different than you guys. The
> > > evolution of a function like the flagellar motility system would have
> > > to have created such a system via a series of relatively small
> > > mutations over time - with each step being beneficially functional and
> > > selectable. I'm not suggesting that evolution forces new features to
> > > appear in any sort of unusual way. I'm suggesting that new functional
> > > features simply didn't appear in the manner that *you* suggest they
> > > appeared.
> >
> > I'm suggesting they appeared by evolution.
>
> Of course you are. And, I'm describing how evolution is supposed to
> work just like you guys.

Sean will disown his strawman thrice before the cock crows if he's
called on it, but as soon as he finds it opportune, he will
re-introduce it right back into the discussion. For example, when
trying to downplay the implications a real-time example of evolution
such as the 2,4-DNT cascade for his claims, he will hasten to point out
that such evolution is no big deal, since the individual enzymes could
be independently useful, and be tacked on to the cascade one step at a
time; apparently, actual examples of "our" version of evolution do not
count as actual examples of "our" version of evolution for Sean.

On the other hand, when trying to play up the complexity of the
flagellum, he will point out that one needs all of the 20-odd
structural proteins, plus the supporting cast of chaperones, transport
proteins, etc., for it to work. Sean won't address (or even
acknowledge unless pointed out) the fact that sub-components of the
flagellum have recognizable independent uses, or that most of the
individual proteins have identifiable non-flagellar homologs, or that
one can propose plausible independent functions for the ancestors of
those proteins. He'll simply insist that somewhere, somehow, there must
be a neutral gap of several thousand base pairs of genetic code that
must be crossed. He will then go right back to arguments that model
his strawman version of evolution, while continuing to deny that this
is the only model he ever presents any actual arguments against. The
only excuse I have seen him give for steadfastly
ignoring "our" version of evolution in any of his calculations of how
long is the failure of scientists to demonstrate any real-time examples
of any of the hypothetical intermediate evolutionary steps. (There are
such examples, but he has excuses to cover those, too.)

> The problem is, the driving forces of
> evolution, i.e., random mutation and natural selection, just can't
> create systems of function that require a minimum of more than a few
> thousand fairly specified bases of DNA.

Ask Sean what this means, and he will at first tell you something like
this:

quote:
As I've told you over and over again, specificity is a description of
the minimum sequence order or limitations of character differences
within a sequence that can be sustained without a complete loss of the
function in question. A function that has greater minimum size
requirements (given a constant degree of specificity) with be at a
higher level of functional complexity. The same is true for a function
that requires a greater degree of specificity (given a constant minimum

size requirement). And, obviously, the same is true for functions that

require both a greater minimum size and specificity requirement.
end quote

So it *looks* like what he means by a few thousand "fairly specified
base pairs" is a sequence of a few thousand base pairs with a
non-trivial degree of *internal* constraint (which, in practice, he
usually expresses as a ratio of sequences that can serve the "function
in question" to those that cannot). And indeed, when giving examples
of what he means by this, whether it be with single enzymes or highly
complex functions like the flagellum, this is more or less how he
represents "functional complexity".

One would think that the same would apply to enzyme cascades such as
the 2,4-DNT cascade, since it lies in complexity somewhere between that
of single enzymes (for which Sean is happy to use the above-described
metric of "functional complexity") and highly complex systems such as
the flagellum (for which Sean is happy to use the above-described
metric of functional complexity).

This impression would be further reinforced by the fact that he offered
this very definition of what he means by "fairly specified base pairs"
when the 2,4-DNT cascade was already under discussion. This impression
would be reinforced further still by the fact that he initially tried
to apply this metric when he thought it could help his case:

quote:
I've already discussed 2,4-DNT with you extensively before. The use of

2,4-DNT involves an enzymatic cascade of just 3 different enzymes
(which does not meet the 3-4k bp minimum by the way in that the
function of these 3 enzymes could probably be coded for by less than a
1k bp sequence). On top of this, the specificity of this system of
function is rather low since the individual enzymes need not be in any
particular orientation with respect to each other in order for the
cascade to proceed. Such enzymatic pathways are made up of fairly
general individual enzymes.
end quote

But press him further on this point, and as soon as he realizes that he
cannot sustain his claim using his own repeatedly-stated definitions
and metrics, he forgets all about minimum size requirements or
constraints on the variability within a minimally-sized sequence. He
wants to talk about everything but: Bernoulli trials, non-existent "in
a row" requirements for genetic sequences, 3D conformations, etc.

So the correct answer to what Sean means by "a minimum of more than a
few thousand fairly specified bases of DNA" is that it means whatever
he needs it to mean at a particular time to help his argument.

Seanpit

unread,

Aug 12, 2006, 10:38:34 PM8/12/06

Marc wrote:

> Here is the thing, Sean - you insist that *something* must be making
> bits of new genetic material beyond a certain size of fragment that you
> think is an upper limit, and you insist that gene duplication can only
> make something that is already there and so there *must* be a designer
> working to make those bigger things, right?

No. That's not what I'm saying at all. I'm not just talking about
making bits of just any kind of new genetic material. I'm talking
about making new genetic material that also results in a novel system
of function that requires more than a few thousand bases at minimum in
order to work. Gene duplication can produce a whole lot of extra
genetic material. That's not the problem. The problem is that gene
duplication cannot produce extra genetic material that also has the
ability to provide a new genetic function to the organism beyond
extremely low levels of functional complexity.

It's like copying a whole page of material out of a book, with a few
extra mutations, and getting another 3-letter word out of the deal. It
is easily to get the equivalent of 3-letter word functions by such
methods. It is another thing entirely to get a new function that
requires an entire page or several pages, at minimum, to code for it.
Gene duplication just doesn't do that for you. It just gives you more
of what you already have. It doesn't produce novel functions or
provide added means of producing novel functions beyond very low levels
of functional complexity.

> So what if you are just a

> little bit wrong about the outcome of gene duplication?

Then I'd be wrong . . . Obviously! Where is your evidence beyond your
just so stories about sequence homologies? Where are your *observable*
demonstrations of the evolution of novel *functions*.

So far, all you've given me as far as observable evidence are sequence
homologies, gene duplications, and the transfer of viral DNA to the
Koala genome. None of these qualify as even a single observation of
the evolution of a new function that wasn't already there.

> What if, as is
> now accepted in science, duplication and divergence is a major force
> in the development of new functions?

I have no problem with gene duplication and divergence. What I do have
a problem with is your notion that gene duplication and divergence
actually give rise to new functions - new functions that require a
minimum of more than a few thousand fairly specified bp of DNA.

> It sort of weakens the need for
> your "designer", right?

Not unless you can show or reasonably explain how gene duplication and
divergence via any kind of random mutation could ever produce a new
functional system that requires more than a few thousand fairly
specified bp of DNA - DNA that produces a protein-based system of
function where more than 1,000 or so residues all work together in a
fairly specified order relative to each other.

Now, don't come back like Von Smith has often tried to do with some
sort of cascading system. Cascading systems of function have very low
overall specificity requirements, relatively speaking. A system that
uses an equivalent minimum number of residues with the additional
requirement of having each of the protein parts in specific arrangement
relative to each other is far more specified and therefore "rare" as
far as its likelihood within sequence space or appearance within a
given genome via random walk (via random mutations) of any kind.

> This post is a copy of your reply to me in a different thread, right?

Yep . . .

> You have a statement top-posted above that would be slightly
> different from the other reply (i.e. it is lacking), but the fact that
> you have copied your entire reply here from another thread (instead
> of just answering my question with an original reply) is analogous
> to a genetic duplication event.

That's true!

> Nice one, Sean!

Thanks!

> Already my reply
> in this thread is different to the comments that I will be making to
> the original version of this message in the other thread. Here, I am
> considering how this very message serves as an illustration of how
> divergence of duplicated material works, while back in the original
> message I will most likely reply about how you should go back and
> read my comments on the basis of the immune system a bit more
> carefully since I still think you fail to grasp them.

I grasp them just fine. Your comments and insights into the immune
system and its supposed evolution really weren't "all that" . . .

> (Of course, not
> making a reply to that thread is also a quite valid example of how
> evolution functions with respect to duplicated material. If the gene
> has a quite essential role, then one of the copies needs to maintain
> that function.)

Of course. You have one copy to maintain a previous function and a new
copy that can explore sequence space via random mutations of some kind.
This still doesn't answer the problem of actually finding a novel
sequences with an attacked beneficial function beyond extremely low
levels of functional complexity . . .

> > Of course you are. And, I'm describing how evolution is supposed to
> > work just like you guys. The problem is, the driving forces of
> > evolution, i.e., random mutation and natural selection, just can't
> > create systems of function that require a minimum of more than a few
> > thousand fairly specified bases of DNA.
>
> You again overlook the other driving force in evolution, gene
> duplication, that answers your conundrum quite clearly.

How did I overlook gene duplication? I discussed gene duplication in
this very post, you just snipped that part of my discussion. Where
have you even attempted to explain how your duplicated gene(s) help in
any significant way in the finding of a novel beneficial functional
system?

> Perhaps you might want to
> read the Annual Review Biochem. paper I cited (which you don't seem
> to have looked at yet), or the paper that John pointed out recently:
> "Allelic divergence precedes and promotes gene duplication"
> Evolution Int J Org Evolution. 2006 May;60(5):881-92. PMID: 16817530

Why don't you explain to me, in your own words if you like or using the
words of the authors of these papers you've listed here, just how gene
duplication helps evolutionary mechanisms find novel systems of
function beyond very low levels of functional complexity?

You seem to be very good at providing irrelevant references. If you
disagree, thinking that these references support your position in any
significant way, then please do explain your own argument here, for
yourself. You can quote any reference you like, but please do actually
present an argument of some kind. Saying over and over again that
"gene duplication solves the problem" isn't helpful. Please do explain
how gene duplication solves the problem. How do these duplicated
portions of DNA find new beneficial functional systems that require
more than a few thousand fairly specified bp of DNA?

> Try these as well:
> "Protein family expansions and biological complexity"
> PLoS Comput Biol. 2006 May;2(5):e48. Epub 2006 May 26.
> PMID: 16733546
> http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=16733546
>
> "Widespread genome duplications throughout the history of
> flowering plants" Genome Res. 2006 Jun;16(6):738-49.
> PMID: 16702410
>
> "Gene duplication and functional divergence of the zebrafish
> insulin-like growth factor 1 receptors."
> FASEB J. 2006 Jun;20(8):1230-2. Epub 2006 May 16.
> PMID: 16705083
>
> "Combinatorial RNA interference in C. elegans reveals that
> redundancy between gene duplicates can be maintained for
> more than 80 million years of evolution."
> Genome Biol. 2006 Aug 2;7(8):R69 [Epub ahead of print]
> PMID: 16884526
>
> "Frequent appearance of novel protein-coding sequences
> by frameshift translation"
> Genomics. 2006 Aug 3; [Epub ahead of print]
> PMID: 16890400
>
> (This last report seems quite interesting - I'd like to hear
> your thoughts about this one after you read it, Sean.)

Frameshift translation does produce novel protein sequences, sometimes
with novel even beneficial functions. The problem is that the functions
produces by such frameshift mutations never require more than a few
hundred fairly specified residues at minimum in order to work to a
minimum selectable level.

For example, the nylonase function has arisen via such a frameshift
mutation in certain bacteria. That is real observable evolution in
action. This novel beneficial function arose via random mutation and
function-based selection. Great! Evolution is a fact! Sure it is.
It is a fact at very low levels of functional complexity. The nylonase
function doesn't require more than a couple hundred fairly specified
residues at minimum. It isn't a very complex function at all. The
nylonase function can be produced by a relatively small loosely
specified single protein enzyme. See the problem?

< snip >

> >You started talking about
> > changes in the pathogen, antigen changes, and the need for an immune
> > system that can compensate for these changes.
>
> Not exactly. The immune response in an individual is more or less
> completely unique, even in twins I would dare say, and it is this
> evolutionary system, going back some 450 million years, that used
> this right from the start - it's one of the very reasons that
> vertebrates
> were able to evolve so well, by a system of self-recognition and the
> ability to respond to non-self and altered-self which evolved alongside
> the established innate immune system. Each individual has their
> strengths and weaknesses in their immune repertoires, but that is
> *NOT EVOLUTION*, it is the result of a system that did evolve but
> the immune response in an individual does *NOT* itself contribute
> to downstream evolution (except in the general sense that some
> components like an given MHC allele or variation in a cytokine or
> receptor can be selected for or against) since the antibody binding
> sites and the TcR binding sites are *NOT* in the germline.

Germline evolution isn't the only type of evolution out there.
Improvements in immune system specificity for a given foreign antigen
most certainly count as real evolution in my book. Just because it
isn't germline evolution doesn't mean it isn't evolution - improved
function via random mutation and function-based selection. That's
exactly what it is. It doesn't have to be passed on to the offpring of
the animal with the immune system in order to be "evolution" - passed
on to generations of immune system cells within the same creature.
That's right, "generations" of somatic cells are produced in the same
creature and the functions of these cells can "evolve" over time. It's
still evolution regardless of the fact that it isn't germline.

> > Of course an entirely
> > new system doesn't need to evolve to detect such antigen changes! If
> > you are talking about the evolution of the immune system, then no, I
> > don't believe that the immune system evolved from ancestor creatures
> > that didn't have an immune system. The minimum coding requirement for
> > a useful immune system is far too complex for evolutionary mechanisms
> > to achieve even in trillions upon trillions of years of time.
>
> Oh, Sean - quit the "trillions of years" stuff. Using such excess of
> scale is trite and shows no appreciation for deep time. A thousand
> million years is an extraordinary long time and there is no need to
> make it sound otherwise.

You don't seem to understand the enormity of the statistics involved
here. A thousand million years is a drop in the proverbial bucket in
comparison to the time that would be needed to evolve across a
non-beneficial gap of only a few dozen fairly specified residue
differences.

> My six year old has a better respect for the
> scale of numbers than that. (He is actually *very* good with numbers,
> perhaps partly from the number of x-box game scores that go up
> into millions and such that he has seen and can grasp quite well.)
> Your use of "trillions" is stupid.

Well, perhaps you can get your six-year-old to help you with the
concept of trillions? - that the answer to some problems does indeed
require much larger numbers than mere billions? You need to expand
your understanding of the true enormity of the gaps involved here Marc.
Even trillions of years are a drop in the bucket. Trillions to the
power of trillions of years don't even do it.

> ......... snp the rest here .....
> (This now becomes a protein domain doing an exon shuffle in the
> duplicated-message/thread model of gene duplication in evolution)

And exon shuffle that ends up producing what? - again?

Von R. Smith

unread,

Aug 13, 2006, 12:31:43 AM8/13/06

Seanpit wrote:
> Marc wrote:
>

<snip>

>
> Now, don't come back like Von Smith has often tried to do with some
> sort of cascading system.

Why shouldn't he? And even if he doesn't, that doesn't mean that I
won't.

> Cascading systems of function have very low
> overall specificity requirements, relatively speaking. A system that
> uses an equivalent minimum number of residues with the additional
> requirement of having each of the protein parts in specific arrangement
> relative to each other is far more specified and therefore "rare" as
> far as its likelihood within sequence space or appearance within a
> given genome via random walk (via random mutations) of any kind.

Here is how Sean has defined specificity "over and over again":

end quote

Specificity is a property of *sequence*, and more particularly an
*internal* and *synchronic* property of a sequence of a given "minimum
size requirement" for a particular "function in question". It is
important to remember that Sean applies this metric not only the
proteins themselves, but to the genetic sequences that code for them.
Sean has never demonstrated that genetic sequences coding for
structural proteins are more *internally* constrained than are genetic
sequences that code for enzymes; he won't even try. He will use change
the subject and throw out a bunch of analogies about the difference
getting two pairs of 6's and getting four 6's in a row, but he won't
tell you what actual property of genetic sequences these analogies are
supposed to represent.

So, by all means, Marc, please do come back like Von Smith and present
some enzyme cascade. You will see for yourself how quickly Sean
abandons his own stated metric for specificity, and tries to talk about
everything but. You will see for yourself Sean's mathematical acumen,
and his stunning grasp of probability and statistics, not to mention
his cogent descriptions of how evolution and genetics actually work.

Seanpit

unread,

Aug 13, 2006, 10:57:45 AM8/13/06

Von R. Smith wrote:

> > Now, don't come back like Von Smith has often tried to do with some
> > sort of cascading system.
>
> Why shouldn't he? And even if he doesn't, that doesn't mean that I
> won't.

That's because you don't seem to grasp the reality that cascading
systems do not require their individual parts to be specifically
arranged relative to each other. For some reason, you can't seem to
comprehend that the lack of a need for this specific arrangement means
that such systems are much less "specified" compared with those systems
that do have this requirement.

> > Cascading systems of function have very low
> > overall specificity requirements, relatively speaking. A system that
> > uses an equivalent minimum number of residues with the additional
> > requirement of having each of the protein parts in specific arrangement
> > relative to each other is far more specified and therefore "rare" as
> > far as its likelihood within sequence space or appearance within a
> > given genome via random walk (via random mutations) of any kind.
>
>
> Here is how Sean has defined specificity "over and over again":
>
> quote:
> As I've told you over and over again, specificity is a description of
> the minimum sequence order or limitations of character differences
> within a sequence that can be sustained without a complete loss of the
> function in question.
> end quote

Exactly. A cascading system does not require all of its parts to be
specifically arranged relative to each other. A system like flagellar
motility, on the other hand, does have this requirement.

> Specificity is a property of *sequence*, and more particularly an
> *internal* and *synchronic* property of a sequence of a given "minimum
> size requirement" for a particular "function in question".

Specificity does just include the 2D order of a sequence Von; it
includes the specific requirements of the 3D order as well.

> It is
> important to remember that Sean applies this metric not only the
> proteins themselves, but to the genetic sequences that code for them.

The final result is the most important thing. You don't seem to
realize that the final result is based on the specific order of the DNA
sequences. Just because you have all the parts of a flagellar system
does not mean that they will self-assemble. They won't. It's like
having all the parts to a watch in a bag and expecting them to
self-assemble into a watch just by shaking the bag. In order for a
bacterium to build a flagellum, it has to produce the parts of the
flagellum in a very specific way. A cascading system doesn't have to
do this. All a cascading system has to do is produce all the parts in
any old way. Clearly, this creates a huge difference in specificity.
I'm simply amazed at your seemingly deliberate blindness in this
regard.

> Sean has never demonstrated that genetic sequences coding for
> structural proteins are more *internally* constrained than are genetic
> sequences that code for enzymes; he won't even try.

Enzymes may be quite highly constrained, individually. However,
enzymatic cascades are not highly constrained collectively. That's the
difference Von. Come on now; this isn't that difficult.

> He will use change
> the subject and throw out a bunch of analogies about the difference
> getting two pairs of 6's and getting four 6's in a row, but he won't
> tell you what actual property of genetic sequences these analogies are
> supposed to represent.

I've explained this to you dozens of times now. The sequences of face
numbers realized on the dice represent sequences of residues of a
protein-based system. If the system requires two separate non-dependent
3aa sequences, such a system of function will be much much easier to
realize in a given genome than a function that requires a single
specific 6aa sequence - just as it is in dice. It is much much easier,
in throwing dice, to realize two independent throws of double sixes
than it is to realize four sixes thrown in a row (regardless of how
many dice you use).

> So, by all means, Marc, please do come back like Von Smith and present
> some enzyme cascade. You will see for yourself how quickly Sean
> abandons his own stated metric for specificity, and tries to talk about
> everything but. You will see for yourself Sean's mathematical acumen,
> and his stunning grasp of probability and statistics, not to mention
> his cogent descriptions of how evolution and genetics actually work.

Tell me Von, which is easier to do, to get two independent double sixes
or 4 sixes in a row? - using however many dice you want . . .

Sean Pitman
www.DetectingDesign.com

Von R. Smith

unread,

Aug 13, 2006, 1:18:00 PM8/13/06

Seanpit wrote:
> Von R. Smith wrote:
>

<snip>

>
> > > Cascading systems of function have very low
> > > overall specificity requirements, relatively speaking. A system that
> > > uses an equivalent minimum number of residues with the additional
> > > requirement of having each of the protein parts in specific arrangement
> > > relative to each other is far more specified and therefore "rare" as
> > > far as its likelihood within sequence space or appearance within a
> > > given genome via random walk (via random mutations) of any kind.
> >
> >
> > Here is how Sean has defined specificity "over and over again":
> >
> > quote:
> > As I've told you over and over again, specificity is a description of
> > the minimum sequence order or limitations of character differences
> > within a sequence that can be sustained without a complete loss of the
> > function in question.
> > end quote
>
> Exactly. A cascading system does not require all of its parts to be
> specifically arranged relative to each other. A system like flagellar
> motility, on the other hand, does have this requirement.

Using a minimally-sized nucleotide sequence in each case, explain how
this distinction manifests itself as a difference in how
internally-constrained the respective sequences are.

>
> > Specificity is a property of *sequence*, and more particularly an
> > *internal* and *synchronic* property of a sequence of a given "minimum
> > size requirement" for a particular "function in question".
>
> Specificity does just include the 2D order of a sequence Von; it
> includes the specific requirements of the 3D order as well.

As you have defined it "over and over again", specificity is strictly a
property of one-dimensional arrays of nucleotides or amino acids. "3D
order" is not a property that such sequences can have; it is a
description of how a particular set of proteins may or may not interact
once they are translated. IOW, it is an aspect of the "function in
question", not of specificity.

I have a sequence of a given size; that sequence either codes for
proteins capable of assuming the right "3D order", or it does not.
Either it codes for a given enzyme cascade, or it does not.
Specificity as you have defined it "over and over again" is a
description of the proportion of possible sequences of said length that
do in either case. That proportion *may or may not* be lower (and
hence the specificity higher) for proteins requiring a particular "3D
order" than it is for proteins that produce a particular enzyme
activity. Which one actually has more specificity is an issue of fact,
not something you get to decide a priori and then use to rationalize
redefining your terms mid-argument.

>
> > It is
> > important to remember that Sean applies this metric not only the
> > proteins themselves, but to the genetic sequences that code for them.
>
> The final result is the most important thing. You don't seem to
> realize that the final result is based on the specific order of the DNA
> sequences.

Perhaps the reason that I do not "realize" this is that I have no idea
what it means. What observable property of a nucleotide sequence does
"specific order" refer to here? What additional constraints does the
need for "3D order" impose on the genetic sequence?

Are you claiming that genes encoding structural proteins *individually*
have greater sequence constraints than do genes encoding enzymes?
(What you write further below suggests that the answer is "no")

Are you saying that genes encoding for structures must appear in a
particular order relative to one another on the genome, whereas those
encoding for enzymes in a cascade do not? (If so, this would only
affect specificity by a maximum factor of N! for N number of individual
components)

Are you saying that they are more constrained on how close or far apart
they can appear on the genome? (This is irrelevant if we are measuring
the specificity of a notional minimum-length sequence, since the
individual components will by definition always be maximally close to
one another)

If the answer to any of these questions is "yes", then I would like to
see a justification for it. If the answer to these questions is "no",
then tell me what the additional constraints on the genetic sequences
coding for structures with "3D order" are that increase their
specificity so much. And please skip the analogies. I want an actual
description of actual properties of actual genetic sequences that
manifest this alleged additional constraint on their internal
variability.

> Just because you have all the parts of a flagellar system
> does not mean that they will self-assemble. They won't.

So tell me what the additional properties are that the coding sequences
for a flagellum have that contribute to self-assembly. Are you talking
about chaperones and transport proteins? Regulatory sequences and the
various classes of promoters? We can figure these into your stated
metric of specificity quite simply.

> It's like
> having all the parts to a watch in a bag and expecting them to
> self-assemble into a watch just by shaking the bag. In order for a
> bacterium to build a flagellum, it has to produce the parts of the
> flagellum in a very specific way. A cascading system doesn't have to
> do this. All a cascading system has to do is produce all the parts in
> any old way. Clearly, this creates a huge difference in specificity.
> I'm simply amazed at your seemingly deliberate blindness in this
> regard.

My "blindness in this regard" hardly seems to be the unique personal
failing you are suggesting it is. Others more knowledgeable on these
topics than either you or myself seem to be similarly blind, judging by
their responses to your arguments. For my part, I attribute tmy
blindness to your utter failure to shed any light on just how the need
for post-translational assembly places additional constraints on the
internal variability of genetic sequences. It is obvious that you
believe that it does, but you have never demonstrated how. All you
offer are analogies about die rolls, marbles, and strings of text.

>
> > Sean has never demonstrated that genetic sequences coding for
> > structural proteins are more *internally* constrained than are genetic
> > sequences that code for enzymes; he won't even try.
>
> Enzymes may be quite highly constrained, individually. However,
> enzymatic cascades are not highly constrained collectively. That's the
> difference Von. Come on now; this isn't that difficult.

What sorts of constraints on internal variability does a
minimally-sized genetic sequence coding for an enzyme cascade lack that
a similar sequence coding for a different type of function have? The
only one I can think of might be the order in which the individual
genes appear, which can affect specificity by a maximum factor of N!,
where N is the number of genes.

Or to ask the question a different way: Suppose I have a
minimally-sized sequence for encoding a "3D" function. Apart from
differences within the individual gene sequences, and in the order in
which those genes appear, what other variables can I change to produce
distinct nucleotide sequences of that length?

Seanpit

unread,

Aug 14, 2006, 10:38:27 AM8/14/06

Von R. Smith wrote:
> Seanpit wrote:
> > Von R. Smith wrote:
> >
>
> <snip>
>
> >
> > > > Cascading systems of function have very low
> > > > overall specificity requirements, relatively speaking. A system that
> > > > uses an equivalent minimum number of residues with the additional
> > > > requirement of having each of the protein parts in specific arrangement
> > > > relative to each other is far more specified and therefore "rare" as
> > > > far as its likelihood within sequence space or appearance within a
> > > > given genome via random walk (via random mutations) of any kind.
> > >
> > >
> > > Here is how Sean has defined specificity "over and over again":
> > >
> > > quote:
> > > As I've told you over and over again, specificity is a description of
> > > the minimum sequence order or limitations of character differences
> > > within a sequence that can be sustained without a complete loss of the
> > > function in question.
> > > end quote
> >
> > Exactly. A cascading system does not require all of its parts to be
> > specifically arranged relative to each other. A system like flagellar
> > motility, on the other hand, does have this requirement.
>
> Using a minimally-sized nucleotide sequence in each case, explain how
> this distinction manifests itself as a difference in how
> internally-constrained the respective sequences are.

Take a system that requires specific orientation of all of its parts
relative to each other. The production of such a system is quite
unique in sequence space. The parts involved could have been arranged
in any myriad number of ways. The fact that they are arranged in such
a way as to produce a specific setup with a specific function requires
a great deal of collective constraint on the system as a whole. An
individual protein does not necessarily fold itself properly. It has
to be folded in the proper way after translation. It then has to be
carried to the proper place and manipulated in the proper way into its
proper position in the system that is being built. This all requires
extraordinarily fine-tuned timing. Such timing is only achieved with
the use of very finely orchestrated production of protein parts in just
the right place and time. Of course, this requires very specific
arrangement of the codes in the underlying DNA. You just can't shift
the codes around and have the system self-assemble properly. The
underlying codes must be specifically arranged relative to all the
other codes for all the other sequences involved.

This is different from the codes for a cascading enzymatic system. The
final product for such a system does not require specific orientation
of each of the enzymes with all the other enzymes. This difference is
not described by a factorial. It is an exponential difference.

Again, you can tell the difference in the functional specificity of a
system most easily by looking at the requirements of the system itself.
The underlying code must be able to produce these very specific
requirements vs. a host of other potential arrangements that it could
have produced.

> > > Specificity is a property of *sequence*, and more particularly an
> > > *internal* and *synchronic* property of a sequence of a given "minimum
> > > size requirement" for a particular "function in question".
> >
> > Specificity does just include the 2D order of a sequence Von; it
> > includes the specific requirements of the 3D order as well.
>
> As you have defined it "over and over again", specificity is strictly a
> property of one-dimensional arrays of nucleotides or amino acids.

First off, nucleotide or residue sequences are not one-dimensional, but
two-dimensional. Secondly, the 2D sequence doesn't do the job. A 2D
residue sequence can be folded in many different ways to form the
functional 3D sequence. It is the specific 3D sequence that actually
carries the function. It is this specific 3D requirement that is
important to system "specificity".

> "3D
> order" is not a property that such sequences can have; it is a
> description of how a particular set of proteins may or may not interact
> once they are translated. IOW, it is an aspect of the "function in
> question", not of specificity.

It isn't just any aspect of the function in question. The specific 3D
order of a system is what gives the function its function. This aspect
of the function in question is specificity - i.e., the specific minimum
3D order required to achieve that specific function. The specific 2D
order of a residue isn't enough. In the end, it is the 3D order that
must be in place.

> I have a sequence of a given size; that sequence either codes for
> proteins capable of assuming the right "3D order", or it does not.

It isn't enough that a specific 2D sequence of residues is produced.
Again, a specific 2D sequence can form a great many different 3D
sequences.

> Either it codes for a given enzyme cascade, or it does not.

The order needed, in the underlying code, is exponentially less
constrained when it comes to coding for an enzymatic cascade vs. a
system of equivalent overall size that also requires specific 3D
arrangement of all of its parts - collectively.

> Specificity as you have defined it "over and over again" is a
> description of the proportion of possible sequences of said length that
> do in either case.

Specificity, as I've defined it, is about the system in question - the
likelihood that the system in question will be realized out of all the
other potential possibilities. Cascading systems, as I've explained to
you exhaustively, are exponentially easier to realize because they do
not have the requirement that all their parts be specifically arranged
with all the other parts.

> That proportion *may or may not* be lower (and
> hence the specificity higher) for proteins requiring a particular "3D
> order" than it is for proteins that produce a particular enzyme
> activity.

You're wrong. Systems that require a specific 3D order require a much
greater underlying specificity of code than do systems that do not
require specific 3D order of all of their collective parts.

> Which one actually has more specificity is an issue of fact,
> not something you get to decide a priori and then use to rationalize
> redefining your terms mid-argument.

That's right. The specificity of a system can be determined quite
consistently by looking at the specific 3D requirements of that system.
I really don't see how you can manage to make this relatively simple
concept so obscure in your own mind.

< snip rest of repetition >

Sean Pitman
www.DetectingDesign.com

Marc

unread,

Aug 14, 2006, 11:14:16 AM8/14/06

Seanpit wrote:

**********************************************
Chez Watt in the "What kind of evolution are you having?" category:

> Germline evolution isn't the only type of evolution out there.
> Improvements in immune system specificity for a given foreign antigen
> most certainly count as real evolution in my book. Just because it
> isn't germline evolution doesn't mean it isn't evolution - improved
> function via random mutation and function-based selection. That's
> exactly what it is. It doesn't have to be passed on to the offpring of
> the animal with the immune system in order to be "evolution" - passed
> on to generations of immune system cells within the same creature.
> That's right, "generations" of somatic cells are produced in the same
> creature and the functions of these cells can "evolve" over time. It's
> still evolution regardless of the fact that it isn't germline.

*********************************************

(signed) marc

Marc

unread,

Aug 14, 2006, 11:11:32 AM8/14/06

Cite me a reference, if you can. (I doubt you can, and "Sean Says So"
just doesn't quite work for me, dude.) You are very good at dissing the
articles cited to you and I can't recall that you have cited *any* work
that supports your views.

> It's like copying a whole page of material out of a book, with a few
> extra mutations, and getting another 3-letter word out of the deal. It
> is easily to get the equivalent of 3-letter word functions by such
> methods. It is another thing entirely to get a new function that
> requires an entire page or several pages, at minimum, to code for it.
> Gene duplication just doesn't do that for you. It just gives you more
> of what you already have. It doesn't produce novel functions or
> provide added means of producing novel functions beyond very low levels
> of functional complexity.

Is that because you say it doesn't? Maybe you can cite evidence?

Every family of proteins is a result of duplications, Sean. That's why
they are found to be in families. How do you think that happened?

Cite me a reference that shows some support for the position you
are taking here. Cite some sort of study that supports what you say.

> > So what if you are just a
> > little bit wrong about the outcome of gene duplication?
>
> Then I'd be wrong . . . Obviously!

But can you accept that you are wrong?

(Reading the papers will help, but it is best done with an open mind.)

Accepting that your model is flawed is a good starting point to
learning what the current scientific viewpoint is (which I'm trying
to point out to you.... remember, it's not just *my* viewpoint here.)

> Where is your evidence beyond your
> just so stories about sequence homologies? Where are your *observable*
> demonstrations of the evolution of novel *functions*.
>
> So far, all you've given me as far as observable evidence are sequence
> homologies, gene duplications, and the transfer of viral DNA to the
> Koala genome. None of these qualify as even a single observation of
> the evolution of a new function that wasn't already there.
>
> > What if, as is
> > now accepted in science, duplication and divergence is a major force
> > in the development of new functions?
>
> I have no problem with gene duplication and divergence. What I do have
> a problem with is your notion that gene duplication and divergence
> actually give rise to new functions - new functions that require a
> minimum of more than a few thousand fairly specified bp of DNA.

You haven't read the review from The AR Biochemistry, 2005, have you?
You really should - I mentioned the section headings in the post
where I first suggested it to you (or maybe the next time).

Maybe you can read this instead (it's available for free - just click!)
"Insights into the coupling of duplication events and macroevolution
from an age profile of animal transmembrane gene families"
PLoS Comput Biol. 2006 Aug 11;2(8):e102. PMID: 16895434
http://mbe.oxfordjournals.org/cgi/reprint/msl085v1

> > It sort of weakens the need for
> > your "designer", right?
>
> Not unless you can show or reasonably explain how gene duplication and
> divergence via any kind of random mutation could ever produce a new
> functional system that requires more than a few thousand fairly
> specified bp of DNA - DNA that produces a protein-based system of
> function where more than 1,000 or so residues all work together in a
> fairly specified order relative to each other.

"Identification and analysis of genes and pseudogenes within
duplicated regions in the human and mouse genomes"
PLoS Comput Biol. 2006 Jun 30;2(6):e76. Epub 2006 May 16.
PMID: 16846249

Abstract:
The identification and classification of genes and pseudogenes
in duplicated regions still constitutes a challenge for standard
automated genome annotation procedures. Using an integrated
homology and orthology analysis independent of current gene
annotation, we have identified 9,484 and 9,017 gene duplicates
in human and mouse, respectively. On the basis of the integrity
of their coding regions, we have classified them into functional
and inactive duplicates, allowing us to define the first consistent
and comprehensive collection of 1,811 human and 1,581 mouse
unprocessed pseudogenes. Furthermore, of the total of 14,172
human and mouse duplicates predicted to be functional genes,
as many as 420 are not included in current reference gene
databases and therefore correspond to likely novel mammalian
genes. Some of these correspond to partial duplicates with less
than half of the length of the original source genes, yet they are
conserved and syntenic among different mammalian lineages.
The genes and unprocessed pseudogenes obtained here will
enable further studies on the mechanisms involved in gene
duplication as well as of the fate of duplicated genes.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16846249

You *really* should go back and re-read that thread more carefully.

Your comments there still need to be addressed. After the degree
of misunderstanding of my post that you showed, you then tried
to say that an immune response "evolves" - which is completely
true in one sense, but totally wrong in the other, and from your
comments you are not too clear about the difference. Evolution
itself resulted in the vertebrate immune system, which does
allow for an antibody response to react to targets with somatic
hypermutation - however such changes do not get passed down
in the course of Evolution. Immune responses are constrained to
within the individual and are not a feature of the germline. Get it?

Your comment from the other thead was (and this is copied....)

"This doesn't mean evolution isn't happening within a given immune
system - even if that information isn't passed on to children and
grandchildren. The evolution taking place here is between generations
of immune system cells."

Something here tells me you are confused about evolution.

> > (Of course, not
> > making a reply to that thread is also a quite valid example of how
> > evolution functions with respect to duplicated material. If the gene
> > has a quite essential role, then one of the copies needs to maintain
> > that function.)
>
> Of course. You have one copy to maintain a previous function and a new
> copy that can explore sequence space via random mutations of some kind.
> This still doesn't answer the problem of actually finding a novel
> sequences with an attacked beneficial function beyond extremely low
> levels of functional complexity . . .

Read the damn literature, dude.

> > > Of course you are. And, I'm describing how evolution is supposed to
> > > work just like you guys. The problem is, the driving forces of
> > > evolution, i.e., random mutation and natural selection, just can't
> > > create systems of function that require a minimum of more than a few
> > > thousand fairly specified bases of DNA.
> >
> > You again overlook the other driving force in evolution, gene
> > duplication, that answers your conundrum quite clearly.
>
> How did I overlook gene duplication? I discussed gene duplication in
> this very post, you just snipped that part of my discussion. Where
> have you even attempted to explain how your duplicated gene(s) help in
> any significant way in the finding of a novel beneficial functional
> system?

"This Post" is a reply from another thread that you have *duplicated*
into this thread because you are a bit lazy and thought it would score
a few cheap points. (I *would* have seen the original and commented
to these points there.) Let's go look.... nope. Can't see any such
discussion. (At the most, you will have just said - without citation -
that duplication does not do anything. Is *that* discussion?)

Maybe you could cite a reference in support of your ideas here.
(Maybe you could read some of the papers that *do not* support
your ideas, too. Oh... you don't like to do that, do you?)

> > Perhaps you might want to
> > read the Annual Review Biochem. paper I cited (which you don't seem
> > to have looked at yet), or the paper that John pointed out recently:
> > "Allelic divergence precedes and promotes gene duplication"
> > Evolution Int J Org Evolution. 2006 May;60(5):881-92. PMID: 16817530
>
> Why don't you explain to me, in your own words if you like or using the
> words of the authors of these papers you've listed here, just how gene
> duplication helps evolutionary mechanisms find novel systems of
> function beyond very low levels of functional complexity?

Here is *another* paper (this one is a review...)

"Gene-balanced duplications, like tetraploidy, provide predictable
drive to increase morphological complexity"
Genome Res. 2006 Jul;16(7):805-14. Review. PMID: 16818725
Abstract:
"Controversy surrounds the apparent rising maximums of morphological
complexity during eukaryotic evolution, with organisms increasing the
number and nestedness of developmental areas as evidenced by
morphological elaborations reflecting area boundaries. No "predictable
drive" to increase this sort of complexity has been reported. Recent
genetic data and theory in the general area of gene dosage effects
has engendered a robust "gene balance hypothesis," with a theoretical
base that makes specific predictions as to gene content changes
following different types of gene duplication. Genomic data from both
chordate and angiosperm genomes fit these predictions: Each
type of duplication provides a one-way injection of a biased set
of genes into the gene pool. Tetraploidies and balanced segments
inject bias for those genes whose products are the subunits of the
most complex biological machines or cascades, like transcription
factors (TFs) and proteasome core proteins. Most duplicate genes
are removed after tetraploidy. Genic balance is maintained by not
removing those genes that are dose-sensitive, which tends to leave
duplicate "functional modules" as the indirect products (spandrels)
of purifying selection. Functional modules are the likely precursors
of coadapted gene complexes, a unit of natural selection. The result
is a predictable drive mechanism where "drive" is used rigorously,
as in "meiotic drive." Rising morphological gain is expected given
a supply of duplicate functional modules. All flowering plants have
survived at least three large-scale duplications/diploidizations over
the last 300 million years (Myr). An equivalent period of tetraploidy
and body plan evolution may have ended for animals 500 million
years ago (Mya). We argue that "balanced gene drive" is a sufficient
explanation for the trend that the maximums of morphological
complexity have gone up, and not down, in both plant and animal
eukaryotic lineages.

> You seem to be very good at providing irrelevant references.

The papers are relevant only when you actually read them.

> If you
> disagree, thinking that these references support your position in any
> significant way, then please do explain your own argument here, for
> yourself. You can quote any reference you like, but please do actually
> present an argument of some kind. Saying over and over again that
> "gene duplication solves the problem" isn't helpful. Please do explain
> how gene duplication solves the problem. How do these duplicated
> portions of DNA find new beneficial functional systems that require
> more than a few thousand fairly specified bp of DNA?

Read the Orengo and Thornton review "Protein families and their
evolution - a structural perspective" Annu Rev Biochem.
2005;74:867-900. PMID: 15954844

These are the sections to look at: "How do changes in domains and
domain partnerships give rise to new protein functions and biological
processes?" and "How does the evolution of protein families influence
the complexity and evolution of organisms?"

Another example...
"Neofunctionalization in vertebrates: the example of retinoic acid
receptors"
PLoS Genet. 2006 Jul;2(7):e102. PMID: 16839186
>From the abstract:
"In this study, we have investigated how gene duplication has affected
both the expression and the ligand-binding specificity of retinoic acid
receptors (RARs), which play a major role in chordate embryonic
development. Mammals have three paralogous RAR genes--RAR
alpha, beta, and gamma--which resulted from genome duplications
at the origin of vertebrates. ...
On the basis of these results together, we suggest that while RAR
beta kept the ancestral RAR role, RAR alpha and RAR gamma
diverged both in ligand-binding capacity and in expression patterns.
We thus suggest that neofunctionalization occurred at both the
expression and the functional levels to shape RAR roles during
development in vertebrates."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16839186

Here is the abstract, since it would seem that you haven't looked at
it.

"Frequent appearance of novel protein-coding sequences by

frameshift translation" Genomics. 2006 Aug 3; PMID: 16890400
Abstract:
"Genomic duplication, followed by divergence, contributes to
organismal evolution. Several mechanisms, such as exon shuffling
and alternative splicing, are responsible for novel gene functions,
but they generate homologous domains and do not usually lead
to drastic innovation. Major novelties can potentially be introduced
by frameshift mutations and this idea can explain the creation of
novel proteins. Here, we employ a strategy using simulated protein
sequences and identify 470 human and 108 mouse frameshift events
that originate new gene segments. No obvious interspecies overlap
was observed, suggesting high rates of acquisition of evolutionary
events. This inference is supported by a deficiency of TpA
dinucleotides in the protein-coding sequences, which decreases
the occurrence of translational termination, even on the complementary
strand. Increased usage of the TGA codon as the termination signal in
newer genes also supports our inference. This suggests that
tolerated frameshift changes are a prevalent mechanism for the
rapid emergence of new genes and that protein-coding sequences
can be derived from existing or ancestral exons rather than from
events that result in noncoding sequences becoming exons."

*************************
CHEZ WATT ALERT:

> Germline evolution isn't the only type of evolution out there.

In the "I understand evolution quite well" category.
***********************************************************

> Improvements in immune system specificity for a given foreign antigen
> most certainly count as real evolution in my book. Just because it
> isn't germline evolution doesn't mean it isn't evolution - improved
> function via random mutation and function-based selection. That's
> exactly what it is. It doesn't have to be passed on to the offpring of
> the animal with the immune system in order to be "evolution" - passed
> on to generations of immune system cells within the same creature.
> That's right, "generations" of somatic cells are produced in the same
> creature and the functions of these cells can "evolve" over time. It's
> still evolution regardless of the fact that it isn't germline.

Hell - chez watt the whole passage !!!!! (I'd better re-post this.)

**********************************

A lesson in statistics from you is a lesson I do not need, seeing
how completely wrong you are in a number of areas. ("Trillions"?)

> > My six year old has a better respect for the
> > scale of numbers than that. (He is actually *very* good with numbers,
> > perhaps partly from the number of x-box game scores that go up
> > into millions and such that he has seen and can grasp quite well.)
> > Your use of "trillions" is stupid.
>
> Well, perhaps you can get your six-year-old to help you with the
> concept of trillions? - that the answer to some problems does indeed
> require much larger numbers than mere billions? You need to expand
> your understanding of the true enormity of the gaps involved here Marc.
> Even trillions of years are a drop in the bucket. Trillions to the
> power of trillions of years don't even do it.

Again, your use of such exaggeration is noted and adds to the
weakness of your argument - that it just seems "wrong" to you
even though evolution occurred in the time frame now known to us.
(That is, it just took 0.0038 of your first trillion years.)

> > ......... snp the rest here .....
> > (This now becomes a protein domain doing an exon shuffle in the
> > duplicated-message/thread model of gene duplication in evolution)
>
> And exon shuffle that ends up producing what? - again?

Reactivating pseudogenes to keep the MHC class II gene number optimal.
http://www.pnas.org/cgi/reprint/103/15/5864 or
http://www.pnas.org/cgi/content/full/103/15/5864

Produce a novel, function gene from ancestral noncoding (junk) DNA
http://www.pnas.org/cgi/content/abstract/103/26/9935

"A possible role of exon-shuffling in the evolution of signal peptides
of human proteins." FEBS Lett. 2006 Mar 6;580(6):1621-4.
PMID: 16487520

And how about the vertebrate nervous system?
"Origin and evolution of the Trk family of neurotrophic receptors"
Mol Cell Neurosci. 2006 Feb;31(2):179-92. Epub 2005 Oct 25. Review.
PMID: 16253518
Abstract:
Among the numerous tyrosine kinase receptors, those belonging
to the Trk family are distinctively involved in the development of
complex traits within the vertebrate nervous system. Until recently,
the lack of a proper Nt/Trk system in invertebrates has lead to
the belief that they were a vertebrate innovation. Recent data,
however, have challenged the field, and proved that bona fide
Trk receptors do exist in invertebrates. Here, we review and
discuss the evolutionary history of the Trk receptor family, and
draw a comprehensive scenario that situates the origin of the
Nt/Trk signalling prior to the origin of vertebrates. Probably, a
ProtoTrk receptor was invented by means of domain and exon
shuffling from pieces of ancient genes, generating the unique
combination of domains found in extant Trk receptors. It is
suggestive to propose that subtle protein mutations, gene
duplications, and co-options in particular territories of a
primitive Nt/Trk system were instrumental to the development
of a complex vertebrate nervous system.

Oh... this report backs you up to some degree - but if you accept
this one, you have to accept all the others, too.
"Modules, multidomain proteins and organismic complexity"
FEBS J. 2005 Oct;272(19):5064-78. PMID: 16176277
Abstract:
Originally the term 'protein module' was coined to distinguish
mobile domains that frequently occur as building blocks of diverse
multidomain proteins from 'static' domains that usually exist only
as stand-alone units of single-domain proteins. Despite the
widespread use of the term 'mobile domain', the distinction
between static and mobile domains is rather vague as it is not
easy to quantify the mobility of domains. In the present work
we show that the most appropriate measure of the mobility of
domains is the number of types of local environments in which
a given domain is present. Ranking of domains with respect
to this parameter in different evolutionary lineages highlighted
marked differences in the propensity of domains to form multidomain
proteins. Our analyses have also shown that there is a correlation
between domain size and domain mobility: smaller domains are
more likely to be used in the construction of multidomain proteins,
whereas larger domains are more likely to be static, stand-alone
domains. It is also shown that shuffling of a limited set of modules
was facilitated by intronic recombination in the metazoan lineage
and this has contributed significantly to the emergence of novel
complex multidomain proteins, novel functions and increased
organismic complexity of metazoa.

"Origin and evolution of new exons in rodents" Genome Res. 2005
Sep;15(9):1258-64. Epub 2005 Aug 18. PMID: 16109974
A quote from the abstract: "Exon shuffling has been universally
observed in the formation of new genes."

"Gene duplication and exon shuffling by helitron-like transposons
generate intraspecies diversity in maize."
Nat Genet. 2005 Sep;37(9):997-1002. PMID: 16056225
A quote from the abstract (note that transposons are at work here):
"Helitrons in maize seem to continually produce new nonautonomous
elements responsible for the duplicative insertion of gene segments
into new locations and for the unprecedented genic diversity."

"Signs of ancient and modern exon-shuffling are correlated to the
distribution of ancient and modern domains along proteins"
J Mol Evol. 2005 Sep;61(3):341-50. PMID: 16034650

Here is another one in your favour, but to accept this you have to
also accept the reports that do not favour your position, OK?
"The rarity of gene shuffling in conserved genes"
Genome Biol. 2005;6(6):R50. PMID: 15960802
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15960802

"Significant expansion of exon-bordering protein domains during
animal proteome evolution"
Nucleic Acids Res. 2005 Jan 7;33(1):95-105. PMID: 15640447
http://nar.oxfordjournals.org/cgi/content/full/33/1/95

(signed) marc

Marc

unread,

Aug 14, 2006, 11:15:47 AM8/14/06

Yeah - my bad. Forgot the subject line change.... D'oh.

Seanpit wrote:

**********************************************
Chez Watt in the "What kind of evolution are you having?" category:

> Germline evolution isn't the only type of evolution out there.

*********************************************

(signed) marc

z

unread,

Aug 15, 2006, 3:21:46 AM8/15/06

On 14 Aug 2006 07:38:27 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

In essence, word salad. If we want to limit the discussion to
protein-protein interactions all we need brownian motion.

> An
>individual protein does not necessarily fold itself properly. It has
>to be folded in the proper way after translation. It then has to be
>carried to the proper place and manipulated in the proper way into its
>proper position in the system that is being built.

For the most part, no. In most proteins the 3D folding patern is
determined solely by the the sequence of the protein.

>extraordinarily fine-tuned timing. Such timing is only achieved with
>the use of very finely orchestrated production of protein parts in just
>the right place and time. Of course, this requires very specific
>arrangement of the codes in the underlying DNA. You just can't shift
>the codes around and have the system self-assemble properly. The
>underlying codes must be specifically arranged relative to all the
>other codes for all the other sequences involved.

Again, word salad. What codes are you talking about? The proteins of
the flagella (for example) self assemble. There is no DNA code post
translation.

>
>This is different from the codes for a cascading enzymatic system. The
>final product for such a system does not require specific orientation
>of each of the enzymes with all the other enzymes. This difference is
>not described by a factorial. It is an exponential difference.

Cascading enzyme systems are coded for linearlly. Orientation of
enzymes is pretty much irrelevant for the the vast majority of
biology. Your point was?

>
>Again, you can tell the difference in the functional specificity of a
>system most easily by looking at the requirements of the system itself.
> The underlying code must be able to produce these very specific
>requirements vs. a host of other potential arrangements that it could
>have produced.
>
>> > > Specificity is a property of *sequence*, and more particularly an
>> > > *internal* and *synchronic* property of a sequence of a given "minimum
>> > > size requirement" for a particular "function in question".
>> >
>> > Specificity does just include the 2D order of a sequence Von; it
>> > includes the specific requirements of the 3D order as well.
>>
>> As you have defined it "over and over again", specificity is strictly a
>> property of one-dimensional arrays of nucleotides or amino acids.
>
>First off, nucleotide or residue sequences are not one-dimensional, but
>two-dimensional. Secondly, the 2D sequence doesn't do the job. A 2D
>residue sequence can be folded in many different ways to form the
>functional 3D sequence. It is the specific 3D sequence that actually
>carries the function. It is this specific 3D requirement that is
>important to system "specificity".

Well, there lies the rub. The majority of 3D folds we info on are
from proteins that are small, and tend to fold on there own. They
also constitute the majority of proteins. Bigger proteins tend to be
concatenations of smaller folding elements- this is not an absolute
howver.

We have fairly large datasets now. It's very clear that there are a
smallish numeber (say ~100) of protein folds that are found commonly
in biological systems. And its quite clear that they can be very
divergent in sequence and still have the same 3D structure.

No, they are asking for the same thing. You are asking for sequential
interaction of either set of enzyme substrates with cognate enzymes,
or asking for proteins to bind to each other.

>
>> That proportion *may or may not* be lower (and
>> hence the specificity higher) for proteins requiring a particular "3D
>> order" than it is for proteins that produce a particular enzyme
>> activity.
>
>You're wrong. Systems that require a specific 3D order require a much
>greater underlying specificity of code than do systems that do not
>require specific 3D order of all of their collective parts.

Perhaps they do if they require an engineering diagram, but not if
they self-assemble. And, as all biology they do so in messy an
ineffcient ways.

>
>> Which one actually has more specificity is an issue of fact,
>> not something you get to decide a priori and then use to rationalize
>> redefining your terms mid-argument.
>
>That's right. The specificity of a system can be determined quite
>consistently by looking at the specific 3D requirements of that system.
>I really don't see how you can manage to make this relatively simple
>concept so obscure in your own mind.

What a horrible conceit.

B Miller

Von R. Smith

unread,

Aug 15, 2006, 8:28:10 AM8/15/06

z wrote:
> On 14 Aug 2006 07:38:27 -0700, "Seanpit"
> <seanpi...@naturalselection.0catch.com> wrote:
>
> >
> >Von R. Smith wrote:
> >> Seanpit wrote:
> >> > Von R. Smith wrote:

<snip>

> > An

> >individual protein does not necessarily fold itself properly. It has
> >to be folded in the proper way after translation. It then has to be
> >carried to the proper place and manipulated in the proper way into its
> >proper position in the system that is being built.
>
> For the most part, no. In most proteins the 3D folding patern is
> determined solely by the the sequence of the protein.
>
> >extraordinarily fine-tuned timing. Such timing is only achieved with
> >the use of very finely orchestrated production of protein parts in just
> >the right place and time. Of course, this requires very specific
> >arrangement of the codes in the underlying DNA. You just can't shift
> >the codes around and have the system self-assemble properly. The
> >underlying codes must be specifically arranged relative to all the
> >other codes for all the other sequences involved.
>
> Again, word salad. What codes are you talking about? The proteins of
> the flagella (for example) self assemble. There is no DNA code post
> translation.

Ah, but Sean thinks that there is. Here is his cue for telling you
that you obviously do not understand the sheer complexity of [whatever
his current Incredulity of the Month happens to be], and for breaking
into his "You can't make a flagellum by shaking up the constituent
proteins in a test-tube" sketch. He actually thinks that there is
some residue of voodoo vitalism needed to account for the phenomenon,
and furthermore insists that said voodoo must somehow be supplied by
the DNA.

He won't tell you exactly what that voodoo is, however, nor where it
resides in the DNA, nor how he knows that that's where it resides; for
somebody who likes to complain so much about being misunderstood, he
can be very coy and vague about his pet ideas. I keep suggesting
things like regulatory sequences, and the genes for things like
chaperones and transport proteins, but I guess that isn't voodoo enough
for Dr. Pitman.

<snip>

>
> >
> >> Specificity as you have defined it "over and over again" is a
> >> description of the proportion of possible sequences of said length that
> >> do in either case.
> >
> >Specificity, as I've defined it, is about the system in question - the
> >likelihood that the system in question will be realized out of all the
> >other potential possibilities. Cascading systems, as I've explained to
> >you exhaustively, are exponentially easier to realize because they do
> >not have the requirement that all their parts be specifically arranged
> >with all the other parts.
>
> No, they are asking for the same thing. You are asking for sequential
> interaction of either set of enzyme substrates with cognate enzymes,
> or asking for proteins to bind to each other.

Thank you. This is a point I had been thinking about bringing up, but
just never got around to. The distinction between "3D orientation" wrt
a metabolite vs. "3D orientation" wrt other proteins produced by the
organism strikes me as a fairly weak basis for insisting on some
exponential difference in complexity, especially when Sean insists that
other types of protein-protein interactions (such as the interactions
between antigens and antibodies) are mere instances of
"template-matching", and hence easy to evolve.

Somebody needs to point out that when Sean writes of a "cascading
function", what he actually seems to mean is something like "metabolic
pathway". Blood-clotting is a "cascading function", but it involves
plenty of internal protein-protein interactions. AIUI, so are some
aspects of genetic expression for the parts of a flagellum, for that
matter. But I'm a layman, so I won't try to delve too deeply into what
is or is not proper terminology.

Seanpit

unread,

Aug 15, 2006, 10:52:32 AM8/15/06

z wrote:

> >Take a system that requires specific orientation of all of its parts
> >relative to each other. The production of such a system is quite
> >unique in sequence space. The parts involved could have been arranged
> >in any myriad number of ways. The fact that they are arranged in such
> >a way as to produce a specific setup with a specific function requires
> >a great deal of collective constraint on the system as a whole.
>
> In essence, word salad. If we want to limit the discussion to
> protein-protein interactions all we need brownian motion.

Not true . . . Brownian motion isn't enough to assemble the parts of a
flagellar motility system even if all the parts are there at the same
time.

> > An
> >individual protein does not necessarily fold itself properly. It has
> >to be folded in the proper way after translation. It then has to be
> >carried to the proper place and manipulated in the proper way into its
> >proper position in the system that is being built.
>
> For the most part, no. In most proteins the 3D folding patern is
> determined solely by the the sequence of the protein.

Many proteins require other proteins to fold them properly. This is
true of many of the proteins in the flagellar motility system. They
simply do not fold, unfold, and refold properly by themselves.

> >extraordinarily fine-tuned timing. Such timing is only achieved with
> >the use of very finely orchestrated production of protein parts in just
> >the right place and time. Of course, this requires very specific
> >arrangement of the codes in the underlying DNA. You just can't shift
> >the codes around and have the system self-assemble properly. The
> >underlying codes must be specifically arranged relative to all the
> >other codes for all the other sequences involved.
>
> Again, word salad. What codes are you talking about? The proteins of
> the flagella (for example) self assemble. There is no DNA code post
> translation.

You are again mistaken. The proteins of the flagella do not
self-assemble properly into a flagellar motility system if they are
simply put in the same place at the same time. The specific order of
their formation is vital to the assembly process.

> >This is different from the codes for a cascading enzymatic system. The
> >final product for such a system does not require specific orientation
> >of each of the enzymes with all the other enzymes. This difference is
> >not described by a factorial. It is an exponential difference.
>
> Cascading enzyme systems are coded for linearlly. Orientation of
> enzymes is pretty much irrelevant for the the vast majority of
> biology. Your point was?

That's my point. Orientation of enzymes in an enzymatic cascade,
relative to the other enzymes in the cascade, is not require for the
function of the cascade to work. This is not true of the systems like
the flagellar motility system where all the individual parts do require
orientation relative to all the other parts.

> >Again, you can tell the difference in the functional specificity of a
> >system most easily by looking at the requirements of the system itself.
> > The underlying code must be able to produce these very specific
> >requirements vs. a host of other potential arrangements that it could
> >have produced.
> >
> >> > > Specificity is a property of *sequence*, and more particularly an
> >> > > *internal* and *synchronic* property of a sequence of a given "minimum
> >> > > size requirement" for a particular "function in question".
> >> >
> >> > Specificity does just include the 2D order of a sequence Von; it
> >> > includes the specific requirements of the 3D order as well.
> >>
> >> As you have defined it "over and over again", specificity is strictly a
> >> property of one-dimensional arrays of nucleotides or amino acids.
> >
> >First off, nucleotide or residue sequences are not one-dimensional, but
> >two-dimensional. Secondly, the 2D sequence doesn't do the job. A 2D
> >residue sequence can be folded in many different ways to form the
> >functional 3D sequence. It is the specific 3D sequence that actually
> >carries the function. It is this specific 3D requirement that is
> >important to system "specificity".
>
> Well, there lies the rub. The majority of 3D folds we info on are
> from proteins that are small, and tend to fold on there own. They
> also constitute the majority of proteins. Bigger proteins tend to be
> concatenations of smaller folding elements- this is not an absolute
> howver.

We are talking about systems of function here. Sure, relatively simple
systems of function that only require a single small protein sequence
aren't much of a problem. However, when it comes to more complex
systems of function, functions that require multiple proteins all
working together in a specific arrangement with each other at the same
time, then you start running into a few problems when it comes to
evolvability. The size and specificity of such multiprotein systems
makes them extremely rare and therefore unlikely to find in the
potential of sequence space.

> We have fairly large datasets now. It's very clear that there are a
> smallish numeber (say ~100) of protein folds that are found commonly
> in biological systems. And its quite clear that they can be very
> divergent in sequence and still have the same 3D structure.

That's also true. However, when it comes to higher and higher levels
of minimum system requirements the non-beneficial ways in which these
"smallish" number of folds can be arranged relative to each other
increases exponentially faster than the very small number of ways that
will actually work to perform a given function - like flagellar
motility.

> >> "3D

I'm asking for a what it takes to achieve a particular function.
Functions that do not require their parts to be in a specific
arrangement with each other are much much easier to evolve,
exponentially so, than those function that do require specific
arrangement of each of their parts with all the other parts in the
system.

> >> That proportion *may or may not* be lower (and
> >> hence the specificity higher) for proteins requiring a particular "3D
> >> order" than it is for proteins that produce a particular enzyme
> >> activity.
> >
> >You're wrong. Systems that require a specific 3D order require a much
> >greater underlying specificity of code than do systems that do not
> >require specific 3D order of all of their collective parts.
>
> Perhaps they do if they require an engineering diagram, but not if
> they self-assemble. And, as all biology they do so in messy an
> ineffcient ways.

You're quite mistaken. Such higher-level systems of function, like the
flagellar motility system, do not simply self-assemble even if all the
needed parts are put together in the same place at the same time. It
is like doing a chemistry experiment. If you don't add and remove the
chemicals in the proper way at the proper time, your experiment will
fail. The same thing is true when it comes to building a multiprotein
system of function in a living thing. The parts simple do not
self-assemble outside of proper finely tuned timing.

> >> Which one actually has more specificity is an issue of fact,
> >> not something you get to decide a priori and then use to rationalize
> >> redefining your terms mid-argument.
> >
> >That's right. The specificity of a system can be determined quite
> >consistently by looking at the specific 3D requirements of that system.
> >I really don't see how you can manage to make this relatively simple
> >concept so obscure in your own mind.
>
> What a horrible conceit.

What deliberate blindness . . .

> B Miller

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 15, 2006, 11:11:38 AM8/15/06

Von R. Smith wrote:

> > Again, word salad. What codes are you talking about? The proteins of
> > the flagella (for example) self assemble. There is no DNA code post
> > translation.
>
> Ah, but Sean thinks that there is.

What are you talking about? I never said that there was DNA post
translation. However, there most certainly is DNA control post
translation. DNA controls not only the production of the protein parts
of a system, but also the timing of formation, location, and removal of
the protein parts, which is vital to proper assembly.

> Here is his cue for telling you
> that you obviously do not understand the sheer complexity of [whatever
> his current Incredulity of the Month happens to be], and for breaking
> into his "You can't make a flagellum by shaking up the constituent
> proteins in a test-tube" sketch. He actually thinks that there is
> some residue of voodoo vitalism needed to account for the phenomenon,
> and furthermore insists that said voodoo must somehow be supplied by
> the DNA.

Do you really think a flagellar motility system would self assembly
simply by having all the parts in the same place at the same time? -
letting them interact randomly via Brownian motion? If so, you are
quite mistaken.

> He won't tell you exactly what that voodoo is, however, nor where it
> resides in the DNA, nor how he knows that that's where it resides; for
> somebody who likes to complain so much about being misunderstood, he
> can be very coy and vague about his pet ideas. I keep suggesting
> things like regulatory sequences, and the genes for things like
> chaperones and transport proteins, but I guess that isn't voodoo enough
> for Dr. Pitman.

Regulatory sequences are in fact quite important to the process, as are
genes for chaperones, as are feedback loops, etc. The point is that
the final product requires specific 3D arrangement and will not work if
any other 3D arrangement of the residues is in fact realized. The
problem with this is that it is in fact possible to realize any other
3D arrangement within sequence space. Being able to land on one
specific arrangement requires very high-level specificity -
exponentially higher than a cascading system requires.

> <snip>
>
> >
> > >
> > >> Specificity as you have defined it "over and over again" is a
> > >> description of the proportion of possible sequences of said length that
> > >> do in either case.
> > >
> > >Specificity, as I've defined it, is about the system in question - the
> > >likelihood that the system in question will be realized out of all the
> > >other potential possibilities. Cascading systems, as I've explained to
> > >you exhaustively, are exponentially easier to realize because they do
> > >not have the requirement that all their parts be specifically arranged
> > >with all the other parts.
> >
> > No, they are asking for the same thing. You are asking for sequential
> > interaction of either set of enzyme substrates with cognate enzymes,
> > or asking for proteins to bind to each other.
>
> Thank you. This is a point I had been thinking about bringing up, but
> just never got around to. The distinction between "3D orientation" wrt
> a metabolite vs. "3D orientation" wrt other proteins produced by the
> organism strikes me as a fairly weak basis for insisting on some
> exponential difference in complexity, especially when Sean insists that
> other types of protein-protein interactions (such as the interactions
> between antigens and antibodies) are mere instances of
> "template-matching", and hence easy to evolve.

I simply can't believe that you don't see the significance, when it
comes to specificity, between a system that does not require its parts
to be in a specific orientation with each other as compared to a system
that does require this limitation. Come on now. This is a huge
difference. It really is like the difference between rolling double
sixes twice and rolling double sixes twice in a row.

> Somebody needs to point out that when Sean writes of a "cascading
> function", what he actually seems to mean is something like "metabolic
> pathway". Blood-clotting is a "cascading function", but it involves
> plenty of internal protein-protein interactions.

Blood clotting is a cascading system of function that does involve a
great many protein-protein interactions. However, it does not require
all of the parts of the cascade to interact with each other in a
specific 3D orientation at the same time. That's the difference
between a blood clotting cascade and a flagellar motility system. This
difference creates a truly exponential difference in evolvability.

> AIUI, so are some
> aspects of genetic expression for the parts of a flagellum, for that
> matter. But I'm a layman, so I won't try to delve too deeply into what
> is or is not proper terminology.

The flagellar system of motility will not work as a motility system
unless a great many of its residue subparts are specifically arranged
relative to all the other residues in 3D space at the same time. That
requires a very high degree of overall system specificity -
exponentially greater than that required by a cascading system.

Sean Pitman
www.DetectingDesign.com

r norman

unread,

Aug 15, 2006, 11:19:22 AM8/15/06

On 15 Aug 2006 07:52:32 -0700, "Seanpit"

<seanpi...@naturalselection.0catch.com> wrote:
>
>z wrote:
>
>> >Take a system that requires specific orientation of all of its parts
>> >relative to each other. The production of such a system is quite
>> >unique in sequence space. The parts involved could have been arranged
>> >in any myriad number of ways. The fact that they are arranged in such
>> >a way as to produce a specific setup with a specific function requires
>> >a great deal of collective constraint on the system as a whole.
>>
>> In essence, word salad. If we want to limit the discussion to
>> protein-protein interactions all we need brownian motion.
>
>Not true . . . Brownian motion isn't enough to assemble the parts of a
>flagellar motility system even if all the parts are there at the same
>time.

Brownian motion combined with selective protein-protein binding sites
will do it. That is sort of comparable to saying that random mutation
alone won't make evolution work but random mutation plus selection
will. Separate protein molecules "spontaneously aggregate" into
assemblages, something that can be demonstrated easily in a test tube

>> > An
>> >individual protein does not necessarily fold itself properly. It has
>> >to be folded in the proper way after translation. It then has to be
>> >carried to the proper place and manipulated in the proper way into its
>> >proper position in the system that is being built.
>>
>> For the most part, no. In most proteins the 3D folding patern is
>> determined solely by the the sequence of the protein.
>
>Many proteins require other proteins to fold them properly. This is
>true of many of the proteins in the flagellar motility system. They
>simply do not fold, unfold, and refold properly by themselves.

This is irrelevant to the overall concept. Not all proteins require
other proteins to fold. It is not known whether the original proteins
involved in the ancestral bacterial flagellum needed them. But even
so, that just means that a few more proteins are needed to produce the
complete assemblage.

>> >extraordinarily fine-tuned timing. Such timing is only achieved with
>> >the use of very finely orchestrated production of protein parts in just
>> >the right place and time. Of course, this requires very specific
>> >arrangement of the codes in the underlying DNA. You just can't shift
>> >the codes around and have the system self-assemble properly. The
>> >underlying codes must be specifically arranged relative to all the
>> >other codes for all the other sequences involved.
>>
>> Again, word salad. What codes are you talking about? The proteins of
>> the flagella (for example) self assemble. There is no DNA code post
>> translation.
>
>You are again mistaken. The proteins of the flagella do not
>self-assemble properly into a flagellar motility system if they are
>simply put in the same place at the same time. The specific order of
>their formation is vital to the assembly process.

A specific ordering sequence can be part of the binding site
properties. Once one pair of proteins binds, it changes the protein
to allow the next binding steps to occur. The G-protein-receptor
G-protein complex goes through exactly such a sequence to produce its
action.

>> >This is different from the codes for a cascading enzymatic system. The
>> >final product for such a system does not require specific orientation
>> >of each of the enzymes with all the other enzymes. This difference is
>> >not described by a factorial. It is an exponential difference.
>>
>> Cascading enzyme systems are coded for linearlly. Orientation of
>> enzymes is pretty much irrelevant for the the vast majority of
>> biology. Your point was?
>
>That's my point. Orientation of enzymes in an enzymatic cascade,
>relative to the other enzymes in the cascade, is not require for the
>function of the cascade to work. This is not true of the systems like
>the flagellar motility system where all the individual parts do require
>orientation relative to all the other parts.

A lot of protein binding steps require 'proper orientation' to
function. Molecules are rather active little thingies moving around
and rotating at rather high speeds. A molecule can bind partially at
a site which allows it to swivel into proper position to bind more
fully.

There is so much wrong here it is difficult to know where to begin.
Was the original bacterial flagellum system as complex as the current
one? (To what extent is the system 'irreducible' if at all). You are
in the mode of multiplying small probabilities to get such a tiny
number that you can prove the final event to be impossible. That
argument has been shown repeatedly to be wrong because the events
involved are not independent so that the probabilities don't multiply.
There are other reasons why the "sequence space" and "probability
calculation" argument fails utterly.

What incredible ignorance.

Von R. Smith

unread,

Aug 16, 2006, 11:35:18 AM8/16/06

Seanpit wrote:
> Von R. Smith wrote:
>
> > > Again, word salad. What codes are you talking about? The proteins of
> > > the flagella (for example) self assemble. There is no DNA code post
> > > translation.
> >
> > Ah, but Sean thinks that there is.
>
> What are you talking about? I never said that there was DNA post
> translation. However, there most certainly is DNA control post
> translation. DNA controls not only the production of the protein parts
> of a system, but also the timing of formation, location, and removal of
> the protein parts, which is vital to proper assembly.

IOW you think that there is DNA code post-translation.

>
> > Here is his cue for telling you
> > that you obviously do not understand the sheer complexity of [whatever
> > his current Incredulity of the Month happens to be], and for breaking
> > into his "You can't make a flagellum by shaking up the constituent
> > proteins in a test-tube" sketch. He actually thinks that there is
> > some residue of voodoo vitalism needed to account for the phenomenon,
> > and furthermore insists that said voodoo must somehow be supplied by
> > the DNA.
>
> Do you really think a flagellar motility system would self assembly
> simply by having all the parts in the same place at the same time? -
> letting them interact randomly via Brownian motion? If so, you are
> quite mistaken.

I see. So tell me exactly what else is needed that only DNA can
supply. Tell me where it is on the DNA, how you think it works, and
what additional constraints it places on sequence variability (thus
increasing specificity as you have defined it "over and over again").
I don't want another analogy. I want an actual description of an
actual difference in genetic sequence.

>
> > He won't tell you exactly what that voodoo is, however, nor where it
> > resides in the DNA, nor how he knows that that's where it resides; for
> > somebody who likes to complain so much about being misunderstood, he
> > can be very coy and vague about his pet ideas. I keep suggesting
> > things like regulatory sequences, and the genes for things like
> > chaperones and transport proteins, but I guess that isn't voodoo enough
> > for Dr. Pitman.
>
> Regulatory sequences are in fact quite important to the process, as are
> genes for chaperones, as are feedback loops, etc. The point is that
> the final product requires specific 3D arrangement and will not work if
> any other 3D arrangement of the residues is in fact realized. The
> problem with this is that it is in fact possible to realize any other
> 3D arrangement within sequence space. Being able to land on one
> specific arrangement requires very high-level specificity -
> exponentially higher than a cascading system requires.

And yet, for all your repeated assertions and assurances on this
matter, and in spite of my repeated requests, you have yet to describe
one actual additional constraint that this places on genetic sequences.

Tell me what the difference is. Tell me where it is. The only
paramters of sequence variability that I can think of for a genetic
sequence of a given length are:

the internal sequences of the individual genes;
the order in which they appear;
their locations along the overall sequence length;
the internal sequences of any "dead space" between the genes.

Tell me which parameters of sequence variability are substantially
different, and your basis for thinking that they must be different.

> It really is like the difference between rolling double
> sixes twice and rolling double sixes twice in a row.

Ah, so there is the dice role analogy again, with the words "really is"
added for effect. Nice argument.

>
> > Somebody needs to point out that when Sean writes of a "cascading
> > function", what he actually seems to mean is something like "metabolic
> > pathway". Blood-clotting is a "cascading function", but it involves
> > plenty of internal protein-protein interactions.
>
> Blood clotting is a cascading system of function that does involve a
> great many protein-protein interactions. However, it does not require
> all of the parts of the cascade to interact with each other in a
> specific 3D orientation at the same time. That's the difference
> between a blood clotting cascade and a flagellar motility system.

When you're done with your special pleading, tell me exactly what
additional constraints this places on the variability of the genetic
sequences coding for the flagellum

> This
> difference creates a truly exponential difference in evolvability.

The definitions of "specificity" and "functional complexity" that you
have provided "over and over again" are not measurements of
evolvability, and lack much information crucial to the question of
evolvability. That there is some relation between these concepts is
one of the unjustified leaps of your argument.

Von R. Smith

unread,

Aug 16, 2006, 6:04:48 PM8/16/06

You didn't answer the question. I asked you for an explanation of
*how* their constraints were different, not for a longer-winded version
of your assertion that they are. I have asked you repeatedly to
specify just what sequence parameters are more constrained in the case
of a "3D" function than they are in the case of an enzyme cascades, and
to date you have either snipped my queries without comment or given
non-responsive responses like the one above. Do you not understand my
question, or do you just not want to answer it?

>
> > > > Specificity is a property of *sequence*, and more particularly an
> > > > *internal* and *synchronic* property of a sequence of a given "minimum
> > > > size requirement" for a particular "function in question".
> > >
> > > Specificity does just include the 2D order of a sequence Von; it
> > > includes the specific requirements of the 3D order as well.
> >
> > As you have defined it "over and over again", specificity is strictly a
> > property of one-dimensional arrays of nucleotides or amino acids.
>
> First off, nucleotide or residue sequences are not one-dimensional, but
> two-dimensional.

I can only think of two directions in which one can move along a
nucleotide sequence: towards the 5' end and towards the 3' end. There
is no "side to side" or "up and down". That would make the sequences
one-dimensional. What second dimension were you thinking of?

> Secondly, the 2D sequence doesn't do the job. A 2D
> residue sequence can be folded in many different ways to form the
> functional 3D sequence. It is the specific 3D sequence that actually
> carries the function. It is this specific 3D requirement that is
> important to system "specificity".

How does this manifest itself as a constraint on the genetic sequence?
You still haven't explained yourself here. Do you really not
understand what I am asking of you, or do you just not want to answer
the question?

>
> > "3D
> > order" is not a property that such sequences can have; it is a
> > description of how a particular set of proteins may or may not interact
> > once they are translated. IOW, it is an aspect of the "function in
> > question", not of specificity.
>
> It isn't just any aspect of the function in question. The specific 3D
> order of a system is what gives the function its function. This aspect
> of the function in question is specificity - i.e., the specific minimum
> 3D order required to achieve that specific function. The specific 2D
> order of a residue isn't enough. In the end, it is the 3D order that
> must be in place.

OK, but where is this represented on the genetic sequence, and what
sorts of additional constraints does this place on the variability of
said sequence that do not also exist in the case of a metabolic
pathway?

>
> > I have a sequence of a given size; that sequence either codes for
> > proteins capable of assuming the right "3D order", or it does not.
>
> It isn't enough that a specific 2D sequence of residues is produced.
> Again, a specific 2D sequence can form a great many different 3D
> sequences.

So what are the additional requirements, and how do these further
constrain the variability of the sequence?

>
> > Either it codes for a given enzyme cascade, or it does not.
>
> The order needed, in the underlying code, is exponentially less
> constrained when it comes to coding for an enzymatic cascade vs. a
> system of equivalent overall size that also requires specific 3D
> arrangement of all of its parts - collectively.
>
> > Specificity as you have defined it "over and over again" is a
> > description of the proportion of possible sequences of said length that
> > do in either case.
>
> Specificity, as I've defined it, is about the system in question - the
> likelihood that the system in question will be realized out of all the
> other potential possibilities. Cascading systems, as I've explained to
> you exhaustively, are exponentially easier to realize because they do
> not have the requirement that all their parts be specifically arranged
> with all the other parts.

You must have a very different understanding of "explained" than I do.
I have seen you assert this repeatedly, but you have never explained it
to my satisfaction. In your last attempt, you essentially claimed
(without seeming to realize it) that 1 out of every 4 random ~1,300aa
peptide sequences would contain not one, not two, but *three* of the
enzymes in the 2,4-DNT cascade. When I challenged you on this, you
changed the subject.

>
> > That proportion *may or may not* be lower (and
> > hence the specificity higher) for proteins requiring a particular "3D
> > order" than it is for proteins that produce a particular enzyme
> > activity.
>
> You're wrong. Systems that require a specific 3D order require a much
> greater underlying specificity of code than do systems that do not
> require specific 3D order of all of their collective parts.

Prove it. Show me what additional constraints there are on sequence
variability.

>
> > Which one actually has more specificity is an issue of fact,
> > not something you get to decide a priori and then use to rationalize
> > redefining your terms mid-argument.
>
> That's right. The specificity of a system can be determined quite
> consistently by looking at the specific 3D requirements of that system.
> I really don't see how you can manage to make this relatively simple
> concept so obscure in your own mind.

Perhaps it is because you abandon your "relatively simple concept" and
introduce completely different parameters each time you realize that it
will not yield you the conclusions you desire. You define specificity
as constraint on the variability of a sequence. Fine. Explain to me
what additional constraints the "3D requirements" you keep talking
about impose. Show me which sequences they affect, and explain how
they affect them. What is it, exactly, that can vary so much in an
enzyme cascade that cannot vary in a function with "3D requirements"?
What is it, exactly, that must be "in a row" in one genetic sequence,
but not the other?

Seanpit

unread,

Aug 19, 2006, 5:46:06 AM8/19/06

r norman wrote:
> On 15 Aug 2006 07:52:32 -0700, "Seanpit"
> <seanpi...@naturalselection.0catch.com> wrote:
> >
> >z wrote:
> >
> >> >Take a system that requires specific orientation of all of its parts
> >> >relative to each other. The production of such a system is quite
> >> >unique in sequence space. The parts involved could have been arranged
> >> >in any myriad number of ways. The fact that they are arranged in such
> >> >a way as to produce a specific setup with a specific function requires
> >> >a great deal of collective constraint on the system as a whole.
> >>
> >> In essence, word salad. If we want to limit the discussion to
> >> protein-protein interactions all we need brownian motion.
> >
> >Not true . . . Brownian motion isn't enough to assemble the parts of a
> >flagellar motility system even if all the parts are there at the same
> >time.
>
> Brownian motion combined with selective protein-protein binding sites
> will do it. That is sort of comparable to saying that random mutation
> alone won't make evolution work but random mutation plus selection
> will. Separate protein molecules "spontaneously aggregate" into
> assemblages, something that can be demonstrated easily in a test tube

Separate protein molecules may spontaneously aggregate into
assemblages, but they will not spontaneously aggregate into high-level
functional assemblages like a flagellar motility system even if all the
protein parts are in the same place at the same time. It is like
expecting the parts of a watch, if all put into a paper bag and shaken
for a few hours, to self-assemble into a functional watch. It just
won't happen. The parts of a flagellum will not self-assemble outside
of very specific tightly controlled production and manipulation of the
parts at just the right time and place. Timing is everything for the
"proper" assembly of the parts of a flagellum.

If you disagree, I'd be very interested in the basis for your argument
here. Is it really your position that the proteins used for flagellar
assembly would simply self-assemble properly if they were all put in
the same general vicinity at the same time?

> >> > An
> >> >individual protein does not necessarily fold itself properly. It has
> >> >to be folded in the proper way after translation. It then has to be
> >> >carried to the proper place and manipulated in the proper way into its
> >> >proper position in the system that is being built.
> >>
> >> For the most part, no. In most proteins the 3D folding patern is
> >> determined solely by the the sequence of the protein.
> >
> >Many proteins require other proteins to fold them properly. This is
> >true of many of the proteins in the flagellar motility system. They
> >simply do not fold, unfold, and refold properly by themselves.
>
> This is irrelevant to the overall concept. Not all proteins require
> other proteins to fold. It is not known whether the original proteins
> involved in the ancestral bacterial flagellum needed them. But even
> so, that just means that a few more proteins are needed to produce the
> complete assemblage.

Not just a few more proteins, but a few more proteins as well as very
specific timing of production and breakdown of proteins into and out of
solution.

> >> >extraordinarily fine-tuned timing. Such timing is only achieved with
> >> >the use of very finely orchestrated production of protein parts in just
> >> >the right place and time. Of course, this requires very specific
> >> >arrangement of the codes in the underlying DNA. You just can't shift
> >> >the codes around and have the system self-assemble properly. The
> >> >underlying codes must be specifically arranged relative to all the
> >> >other codes for all the other sequences involved.
> >>
> >> Again, word salad. What codes are you talking about? The proteins of
> >> the flagella (for example) self assemble. There is no DNA code post
> >> translation.
> >
> >You are again mistaken. The proteins of the flagella do not
> >self-assemble properly into a flagellar motility system if they are
> >simply put in the same place at the same time. The specific order of
> >their formation is vital to the assembly process.
>
> A specific ordering sequence can be part of the binding site
> properties. Once one pair of proteins binds, it changes the protein
> to allow the next binding steps to occur. The G-protein-receptor
> G-protein complex goes through exactly such a sequence to produce its
> action.

Again, such binding sites are not enough for the proper assembly of
multiprotein systems like the flagellar motility system. Just try and
put all the parts for a flagellum or any higher-level system into
solution at the same time and see what happens. Even if all the
protein parts are there in abundance, they will not self-assembly into
much of anything functionally useful beyond and bunch of sludge.

> >> >This is different from the codes for a cascading enzymatic system. The
> >> >final product for such a system does not require specific orientation
> >> >of each of the enzymes with all the other enzymes. This difference is
> >> >not described by a factorial. It is an exponential difference.
> >>
> >> Cascading enzyme systems are coded for linearlly. Orientation of
> >> enzymes is pretty much irrelevant for the the vast majority of
> >> biology. Your point was?
> >
> >That's my point. Orientation of enzymes in an enzymatic cascade,
> >relative to the other enzymes in the cascade, is not require for the
> >function of the cascade to work. This is not true of the systems like
> >the flagellar motility system where all the individual parts do require
> >orientation relative to all the other parts.
>
> A lot of protein binding steps require 'proper orientation' to
> function. Molecules are rather active little thingies moving around
> and rotating at rather high speeds. A molecule can bind partially at
> a site which allows it to swivel into proper position to bind more
> fully.

The problem is that there are so many different ways that the parts of
a flagellar system could bind to each other if they were all put in the
same place at the same time. Again, they simply will not bind to each
other in one specific way to self-assemble a functional flagellar
system of motility. It just won't happen outside of very tightly
controlled timing. It is like a very delicate pathway in the synthesis
of a specific complex molecule in the laboratory. Simply putting all
the right ingredients together at the same time won't do the trick.
They have to be added and taken away at just the right time in just the
right order under just the right conditions in order for the final
desired product to be realized. The very same thing is true of the
assembly of a complex functional system like the flagellum.

It seems like flagellar motility of the most basic kind requires at
least 30,000 fairly specified bp of DNA coding for a system that
requires the specific arrangement of over 20 different proteins
relative to each other. If you can think of a way to build a flagellar
*motility* system with significantly less than this, I'd be most
interested.

>You are
> in the mode of multiplying small probabilities to get such a tiny
> number that you can prove the final event to be impossible. That
> argument has been shown repeatedly to be wrong because the events
> involved are not independent so that the probabilities don't multiply.

Interesting . . . Please do explain your notion of the statistics
involved. Please do explain to me how events that are not independent
(i.e., events that are *dependent* on each other) have a probability of
occurrence that is not based on multiplying the probabilities of each
individual event with each other?

For example, what is the probability of flipping a quarter and landing
it on heads 3 times in a row? Is it not 1/2 x 1/2 x 1/2 = 1/8?

The events involved are not independent, that's true. They are
dependent. They must produce a system with specific arrangement of
multiple copies of over 20 different proteins - to include the specific
arrangement of the hundreds of residues that make up each protein with
all the other residues in the system. This means that the
probabilities do indeed multiply.

It's like the number of rolls needed to roll two double sixes
*independent* of each other vs. two double sixes in a row. It's the
odds of getting two specific 3-letter sequence vs. one six-letter
sequence - or the odds of getting two specific yet independent 3-codon
sequences vs. one specific 6-codon sequence. It is much much easier to
get the former vs. the latter - exponentially so.

If you disagree, I'd be most interested in how you would calculate the
odds in this case. Please do detail your reasoning here. Thanks.

> There are other reasons why the "sequence space" and "probability
> calculation" argument fails utterly.

LOL - Such as? . . .

; )

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 19, 2006, 5:56:51 AM8/19/06

Sure there's a trend. The trend is to published papers based on
sequence comparisons alone. None of these papers discuss *observable*
evolution of new functions based on gene duplication or any other type
of genetic change or mutation.

Why do you keep talking about gene duplication like I don't accept it?
As I've told you over and over again, I have no problem with gene
duplication - or even genome duplication. What I have a problem with
is the notion that gene duplication somehow makes it easy for evolution
to find novel systems of function beyond very low levels of functional
complexity.

As far as I can tell, this notion of yours is simply an unsupported and
statistically untenable assertion - a "just so story" at best. These
stories are based on absolutely nothing more than the notion that
sequence similarities necessitate common descent via random mutation
and natural selection. This notion just isn't valid without a
reasonable mechanism. The ToE doesn't have one. Gene duplication isn't
the magic bullet. It just makes more of what is already there. It may
free up the extra copy to undergo a bit of random walk/sampling within
sequence space, but this just isn't going to do much as far as finding
new functions at even moderately higher levels of minimum size and
specificity requirements this side of a practical eternity of time.

Seanpit

unread,

Aug 19, 2006, 6:05:29 AM8/19/06

Tell me Marc, what is your definition of "evolution". Some people
define evolution as any change over time. Some people definte it as a
functional change over time. How do you define the term "evolution"?
Can the function of a single cell "evolve"?

Do antibodies undergo random changes that are preferentially
selectable, based on functional differences, over generations of immune
cells? How is this not a type of evolution? A new function is realized
over time via random mutation and function-based selection - right?
Are you really arguing that because this function isn't passed on to
the next human generation via coding changes in the gametes means that
it isn't a type of evolution at all? Really?

I think many, even on your own side in this forum, would disagree with
you on this one. I've had extensive discussions in this forum on the
topic of antibody "evolution" and you are the first to argue with me
that the functional changes of antibodies over time don't count as any
form of evolution.

Seanpit

unread,

Aug 19, 2006, 6:06:28 AM8/19/06

Marc wrote:
> Yeah - my bad. Forgot the subject line change.... D'oh.
>

> Seanpit wrote:
>
> **********************************************
> Chez Watt in the "What kind of evolution are you having?" category:

> (signed) marc

Sean Pitman
www.DetectingDesign.

> (signed) marc

r norman

unread,

Aug 19, 2006, 7:28:10 AM8/19/06

On 19 Aug 2006 02:46:06 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

>Please do explain to me how events that are not independent
>(i.e., events that are *dependent* on each other) have a probability of
>occurrence that is not based on multiplying the probabilities of each
>individual event with each other?
>
>For example, what is the probability of flipping a quarter and landing
>it on heads 3 times in a row? Is it not 1/2 x 1/2 x 1/2 = 1/8?
>

What is the probability of flipping a quarter having heads on the
top? It is 1/2. What is the probability of flipping a quarter and
having tails on the bottom? It is 1/2. What is the probability of
flipping and quarter and finding both heads on top and tails on
bottom? Obviously it must be 1/2 x 1/2 = 1/4, the same as the
probability of flipping a quarter and finding head on top and heads on
bottom.

Somehow, it seems that this must be wrong. I can't quite figure out
just why since what you say is obviously The Truth.

Ron O

unread,

Aug 19, 2006, 9:38:16 AM8/19/06

A major boner on Sean's part. What is Sean's explanation for Dembski
not being able to calculate the probabilities for relevant biological
pathways to the creation of the so called IC systems? Dembski was only
able to calculate the probability of the tornado through a junkyard
scenario, and he admitted that it was not biologically relevant. Why
wasn't it bioligically relevant? Someday Sean might be able to buy a
clue, and it would have to be paid for in cash.

Ron Okimoto

Marc

unread,

Aug 19, 2006, 9:48:24 AM8/19/06

Please, Dr. Pitman, you are starting to sound like "UC" here.

Evolution of an immune response in an individual is not the same
as "biological evolution", and I think that you know this quite well.
(You should, anyway, seeing how smart you are and all.)

Which sense of "evolution" are you asking me to define - that
of the immune response or that of a Darwinian nature?

Perhaps your accepting "design" has as much to do with your
confusion about how some people use the different meanings
of "evolution" as anything else. This is of course covered in the
http://www.talkorigins.org/faqs/evolution-definition.html page.

If you are talking about a single cell evolving (as with a single
celled organism), then *yes*, evolution can be taking place. But
you have the expression "function of a single cell evolve" which
implies 1) a cell within a multicellular organism and 2) a task
the cell performs, but not specifically changes in the cell itself.

Evolution is not an attribute of an individual, Dr. Pitman, however
much you swap the definition of the word you are using. Changes
in the gene pool of a population over time are reflected in the
differential appearance of alterations in the characteristics and
traits of individuals coming from that population at different points
of time. Lymphocytes in the vertebrates do not play much of a
role in the shifts to the gene pool. (It is possible that some of the
features of the lymphocyte gene segments that are encoded in the
genome can be selected for or against by pathogens, such as
those producing "superantigens" might have on specific V-beta
chains of the T-cell antigen receptor, so I said "not play much of
a role" but since the actual antigen binding site for antibodies that
B-cells produce or binding sites for the T-cell antigen receptor are
not encoded in the genome, the specific binding sites are never
passed on to offspring.) Because these critical features come from
outside of the genome (so to speak, created by VDJ joining) they
have not been able to be usurped by pathogens the same way
that many other immune system components have been.

> Do antibodies undergo random changes that are preferentially
> selectable, based on functional differences, over generations of immune
> cells?

While the point about "generations of immune cells" is moot (that
the cell divides or not has little to do with this), B-cells do have
somatic hypermutation that can increase the affinity of the binding
site of the antibody in an immune response. That is *not* evolution.

> How is this not a type of evolution?

It is an evolution of an immune response. It is *not* evolution.

> A new function is realized
> over time via random mutation and function-based selection - right?

No. No "new" function is gained. An alteration of an existing binding
site is made which has a potential of increasing the affinity of the
binding of antigen to the antibody (acting as a cell surface receptor
on the B-cell), but that is little more than an improved version of the
antibody binding site that was there before (if it is an improvement,
many changes would not be - but they would not then be useful).

Let me ask you, Dr. Pitman, where the antibody binding pocket
came from in the first place? (The answer was given to you in
the other thread above where you mistook "immune evolution"
in my message for "immune response", but please feel free to
share your understanding of how antibodies get their binding
site in the first place with us, if you can. I also mentioned the
critical "joining" phrase above in this reply, if you need a hint.)

> Are you really arguing that because this function isn't passed on to
> the next human generation via coding changes in the gametes means that
> it isn't a type of evolution at all? Really?

Absolutely. (Well, your wording about this is a bit of a trap - it is
an evolution of a function, but it is *not* evolution. The "a type of"
phrase is your attempt to twist my meaning here - typical of word
games but the lurkers will understand. Your question should be
worded "it isn't a type of biological evolution" because the way
you have put "isn't a type of evolution at all" is just using the
differences in the various meanings of *evolution* to stick one
meaning in where another belongs and to somehow claim a point.)

> I think many, even on your own side in this forum, would disagree with
> you on this one.

Let's have a vote. Please, lurkers and others, indicate here if you
have a disagreement with me about the immune response evolving
in an individual being different to "biological evolution" in the gene
pool of the species over time.

> I've had extensive discussions in this forum on the
> topic of antibody "evolution" and you are the first to argue with me
> that the functional changes of antibodies over time don't count as any
> form of evolution.

Again, you are twisting the wording. There is an evolution of an immune
response. (I've worked in Immunology since before humans were known
to have a second MHC class II locus - part of my contribution as a lab
tech back then was to help put HLA-DQ on the map.) Perhaps you have
not been discussing these points with somebody who has a background
in immunogenetics until now.

The immune response does evolve in an individual, in several ways.
Evolution does take place with respect to a population, and in fact
the features of how the immune response in an individual evolves
has been a focus of evolution in the vertebrates for nearly 500 million
years (or longer, if you consider the innate immune system), but
the definition of "evolution" with respect to an immune response in
an individual is different to that of "evolution" with respect to
species.
(But you knew that, didn't you? Or maybe you don't?)

Since you failed to understand comments about evolution of the
immune system and you are still twisting the meanings around
that reflect on the difference between an "immune response" and
the "immune system", your previous extensive discussions would
no doubt be grounded in error. Don't worry about it now, Dr. Pitman,
because I am here to help you understand what you were taught so
superficially in medical school, and I'm sure my grasp of the
literature
will be put to good use in getting you over this small problem.
(If you will actually read the papers I will be suggesting, that is.)

(signed) marc

Marc

unread,

Aug 19, 2006, 10:00:46 AM8/19/06

Others might say that these papers describe observations of such
evolution quite clearly. There is a great deal of value in the
sequence
data. (Which is why it is such a threat to your way of thinking,
right?)

> Why do you keep talking about gene duplication like I don't accept it?

Because your "accepting" of it is flawed.

> As I've told you over and over again, I have no problem with gene
> duplication - or even genome duplication. What I have a problem with
> is the notion that gene duplication somehow makes it easy for evolution
> to find novel systems of function beyond very low levels of functional
> complexity.

See? That's where your flaw comes in. Put duplication together
with exon shuffling and you have a great deal of new function.

Please tell me that you have considered reading the paper
from the 2005 Annu. Rev. Biochem. - I say considered because
you clearly haven't actually read it, have you?

> As far as I can tell, this notion of yours is simply an unsupported and
> statistically untenable assertion - a "just so story" at best.

It isn't *my* notion, Dr. Pitman, it is the accepted scientific view.

> These
> stories are based on absolutely nothing more than the notion that
> sequence similarities necessitate common descent via random mutation
> and natural selection. This notion just isn't valid without a
> reasonable mechanism. The ToE doesn't have one. Gene duplication isn't
> the magic bullet. It just makes more of what is already there. It may
> free up the extra copy to undergo a bit of random walk/sampling within
> sequence space, but this just isn't going to do much as far as finding
> new functions at even moderately higher levels of minimum size and
> specificity requirements this side of a practical eternity of time.

Can you provide a citation that supports your position here?

(signed) marc

Marc

unread,

Aug 19, 2006, 10:22:58 AM8/19/06

Seanpit wrote:
> Marc wrote:
> > Yeah - my bad. Forgot the subject line change.... D'oh.
> >
> > Seanpit wrote:
> >
> > **********************************************
> > Chez Watt in the "What kind of evolution are you having?" category:
> >
> > > Germline evolution isn't the only type of evolution out there.
> > > Improvements in immune system specificity for a given foreign antigen
> > > most certainly count as real evolution in my book. Just because it
> > > isn't germline evolution doesn't mean it isn't evolution - improved
> > > function via random mutation and function-based selection. That's
> > > exactly what it is. It doesn't have to be passed on to the offpring of
> > > the animal with the immune system in order to be "evolution" - passed
> > > on to generations of immune system cells within the same creature.
> > > That's right, "generations" of somatic cells are produced in the same
> > > creature and the functions of these cells can "evolve" over time. It's
> > > still evolution regardless of the fact that it isn't germline.
> >
> >
> > *********************************************
>
> Tell me Marc, what is your definition of "evolution". Some people
> define evolution as any change over time. Some people definte it as a
> functional change over time. How do you define the term "evolution"?
> Can the function of a single cell "evolve"?

Gee, I seem to have seen these questions before.

Oh - you copied this response and put it here in reply to my
message where I was making sure the "Chex Watt" flag was
in the subject line.

Am I supposed to use this as another example of how
"gene duplication" might work? Thanks for the opportunity...

(snp the rest, since it's in the other reply)

Sean, ... er - Dr. Pitman,
my post was duplicated for a good reason - the flag in the
subject line was needed, Your making identical replies to
both copies of this - like your copy of your reply from one
thread into another last week - is rude. (But that's you...)

I have some *very* high hopes that your passage above which
I have flagged for the next chez watt will make it to the podium.

It would be quite rewarding to have such a blatant, classic type
of misunderstanding of evolution archived on the Chez Watt page
for all time to come. I really hope that between us, you pull in
enough votes to win next month. (Lurkers - I offer beers to those
who will remember to vote for Dr. Pitman's passage on the many
forms of evolution... I would offer massages but nasht0n would
have to give me a refresher course first, and I'm still waiting for
him to read the PLoS-Biology paper on signs of selection in
the human genome).

(signed) marc

Ron O

unread,

Aug 19, 2006, 11:32:19 AM8/19/06

Antibodies that undergo random changes that are selected for based on
functional differences only demonstrates that your bogus notions of
probability are nonsense. It is an example of protein evolution in
real time that anyone can study. It demonstrates that even new enzyme
activities can develop in less than 10E12 events. It demonstrates that
your estimates are bogus and that proteins are more plastic than you
think and that it isn't difficult to evolve new functions from existing
protein sequences.

What an idiot, or is it simple dishonesty this time?

Ron Okimoto

Seanpit

unread,

Aug 19, 2006, 12:00:47 PM8/19/06

Any specific sequence of heads and tails will have the same odds.
That's the whole point. Getting one specific sequence of 3 coin tosses
is 1/8. Do you know of another "truth". You are the one making claims
here that the odds of a specific overall event is not found my
multiplying the odds of the individual *dependent* events. That is
your position - right? If so, please do explain how you arive at this
notion . . .

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 19, 2006, 12:20:03 PM8/19/06

Von R. Smith wrote:

< snip >

> > Do you really think a flagellar motility system would self assembly

> > simply by having all the parts in the same place at the same time? -
> > letting them interact randomly via Brownian motion? If so, you are
> > quite mistaken.
>
>
> I see. So tell me exactly what else is needed that only DNA can
> supply. Tell me where it is on the DNA, how you think it works, and
> what additional constraints it places on sequence variability (thus
> increasing specificity as you have defined it "over and over again").
> I don't want another analogy. I want an actual description of an
> actual difference in genetic sequence.

It seems like you think the underlying code need not be as specified as
the final product. If you want a 1D example, consider your own
"abcdef" sequence yet again. Let's say that this specific sequence is
needed to be in this specific 1D order. Let's also say that each one
of the characters is coded for by the order of another underlying code
- like a series of zeros and ones in computer code. What are the odds
of achieving this final product?

Well, there is only 1 abcdef sequence in 26^6 six character sequences
(308,915,776). Any one of those other 300 million 6-character
sequences could have been produced by the order of the underlying code.
What would it take for the underlying code to specifically end up
producing abcdef?

Well, the underlying code could end up producing two 3-character
sequences where the codes for each 3-character sequence were widely
separated in the "genome"(def . . . abc). The underlying code could
also code for a "chaperone" sequence that would properly link up the
def with the abc to form abcdef. Or, the underlying code could
separately produce each character (a . . . d . . . f . . . e . . . b .
. . c) and then link these up with the help of other sequences.

In the end, what are the odds that the specific sequence abcdef will be
produced by a given underlying computer code "genome"? The odds are
still 1 in over 300 million.

The same is not true of the odds that both abc and def will be produced
in an independent way. The odds that a given underlying computer code
genome will produce both abc and def independent of each other are
exponentially greater than the odds that this genome will produce the
specific sequence abcdef.

In short, the underlying code has to be at least as specified as the
final product. You can't get something specific by using something
that isn't just as specific.

< snip >

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 19, 2006, 12:36:55 PM8/19/06

Marc wrote:

> > > Sean, note that the citations I made in my earlier reply in this
> > > thread (that first paper is *very* interesting, too!) were for articles
> > > that came out in the last week or so. Please read these reports
> > > a.s.a.p. so that next week I can point you to whatever the
> > > forthcoming few papers are that come out on this topic then.
> > >
> > > I'm fairly sure that the next few papers to turn up in a PubMed
> > > search on "duplication divergence" or "gene family" or whatever
> > > will just add to the support of duplication as a mechanism and
> > > there will almost certainly be no papers published next week
> > > that will take away from it. Do you perhaps sense a trend here?
> >
> > Sure there's a trend. The trend is to published papers based on
> > sequence comparisons alone. None of these papers discuss *observable*
> > evolution of new functions based on gene duplication or any other type
> > of genetic change or mutation.
>
> Others might say that these papers describe observations of such
> evolution quite clearly. There is a great deal of value in the
> sequence data. (Which is why it is such a threat to your way of thinking,
> right?)

This discussion isn't over the notion that there are indeed sequence
similarities between different high-level functions. I already know
that. Telling me to read dozens of papers that demonstrate this isn't
going to show me anything that I don't already know.

The question at hand, in case you haven't figured it out yet, concerns
the notion that sequence similarities necessitate common evolutionary
ancestry. That's what the discussion is about Marc. You say that
these similarities are best explained by common descent while I say
that they are best explained by common design when they go beyond very

low levels of functional complexity.

In this particular discussion, you can't use as evidence what we
already both accept as fact. What you have to do is show evidence that
your proposed mechanism, random mutation and natural selection, is in
fact capable of producing higher-level functional systems. Papers that
do not deal with this actual mechanism, choosing instead to rely only
on the assumption that sequence similarities mean common descent, just
don't support your argument in this case.

What you need to do is explain how gene duplication or any other kind
of genetic rearrangement/mutation can possibly produce new functions
that require more than a few thousand fairly specified bases of DNA.
You have yet to do this. You seem to think it enough to just wave your
hand and declare than gene duplications solve all problems. How Marc?
How do gene duplications help to create higher-level functional
systems?

Now, don't come back and list a bunch of references. Explain it to me
in your own words. You can use references to help you, but I want to
see if you understand what you claim to understand. Please do explain
exactly how gene duplication helps evolution find higher level
functional systems in the potential of sequence space.

> > Why do you keep talking about gene duplication like I don't accept it?
>
> Because your "accepting" of it is flawed.

How so? I accept that it happens just fine. I just don't accept that
it produces new higher-level functions. You have yet to show otherwise
beyond your just-so stories and appeals to sequence similarities.

> > As I've told you over and over again, I have no problem with gene
> > duplication - or even genome duplication. What I have a problem with
> > is the notion that gene duplication somehow makes it easy for evolution
> > to find novel systems of function beyond very low levels of functional
> > complexity.
>
> See? That's where your flaw comes in. Put duplication together
> with exon shuffling and you have a great deal of new function.

Oh yeah? How Marc? Any observable examples of this beyond very low
levels of minimum size and specificity requirements?

> Please tell me that you have considered reading the paper
> from the 2005 Annu. Rev. Biochem. - I say considered because
> you clearly haven't actually read it, have you?

Provide your own explanation here Marc. You can use this or whatever
other paper you want to help you. However, simply listing off a bunch
of references is not the same thing as making a good argument of your
own.

> > As far as I can tell, this notion of yours is simply an unsupported and
> > statistically untenable assertion - a "just so story" at best.
>
> It isn't *my* notion, Dr. Pitman, it is the accepted scientific view.

I realize that. It is also your own individual notion. If you really
do understand the basis of this generally accepted notion, then please
do provide an actual explanation of your own. Don't just appeal to
someone else or some other paper. Please do provide your own argument
here.

> > These
> > stories are based on absolutely nothing more than the notion that
> > sequence similarities necessitate common descent via random mutation
> > and natural selection. This notion just isn't valid without a
> > reasonable mechanism. The ToE doesn't have one. Gene duplication isn't
> > the magic bullet. It just makes more of what is already there. It may
> > free up the extra copy to undergo a bit of random walk/sampling within
> > sequence space, but this just isn't going to do much as far as finding
> > new functions at even moderately higher levels of minimum size and
> > specificity requirements this side of a practical eternity of time.
>
> Can you provide a citation that supports your position here?

Of course not because this isn't the mainstream view. It is my own
view. If you really think the mainstream view is correct, please
explain to me in your own words how evolution can produce higher-level
functions with the use of any sort of random genome manipulation
combined with natural selection. Spell it out Marc. How does gene
duplication and exon shuffling end up producing new functions at higher
minimum size and specificity requirements?

r norman

unread,

Aug 19, 2006, 12:47:49 PM8/19/06

On 19 Aug 2006 09:00:47 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

I just did. Read up a few paragraphs. In case you have trouble
scrolling upwards:

Let Pr { X } mean "Probability of getting event X from flipping a coin

Event A: get heads on top.
Pr { A } = 1/2.

Event B: get tails on bottom.
Pr { B } = 1/2.

Event C: get heads on bottom.
Pr { C } = 1/2.

A , B, and C are NOT independent events. Therefore
Pr { A and B } is NOT Pr { A } x Pr { B }
Pr { A and C } is NOT Pr { A] x Pr { C }

Seanpit

unread,

Aug 19, 2006, 12:50:30 PM8/19/06

Marc wrote:

> > Tell me Marc, what is your definition of "evolution". Some people
> > define evolution as any change over time. Some people definte it as a
> > functional change over time. How do you define the term "evolution"?
> > Can the function of a single cell "evolve"?
>
> Please, Dr. Pitman, you are starting to sound like "UC" here.
>
> Evolution of an immune response in an individual is not the same
> as "biological evolution", and I think that you know this quite well.
> (You should, anyway, seeing how smart you are and all.)

It is a type of biological evolution. It meets the definition of change
over time guided by function-based selection.

> Which sense of "evolution" are you asking me to define - that
> of the immune response or that of a Darwinian nature?

I'll accept, as an example of evolution in action, any functional
change over time - regardless of if that function is passed on via
gametes or not. Bacteria divide by clonal cell division and functional
changes in bacteria are considered to be "Darwinian" evolution in
nature. The evolution of immune system cell functions over time is not
fundamentally different than this. Just because the population of
immune system cells eventually dies when it's host dies does not mean
this population didn't undergo real Darwinian-style evolution. It did.

> Perhaps your accepting "design" has as much to do with your
> confusion about how some people use the different meanings
> of "evolution" as anything else. This is of course covered in the
> http://www.talkorigins.org/faqs/evolution-definition.html page.
>
> If you are talking about a single cell evolving (as with a single
> celled organism), then *yes*, evolution can be taking place. But
> you have the expression "function of a single cell evolve" which
> implies 1) a cell within a multicellular organism and 2) a task
> the cell performs, but not specifically changes in the cell itself.

Changes in the task that the immune-system cell performs are indeed
based on changes within the immune-cell itself.

> Evolution is not an attribute of an individual, Dr. Pitman, however
> much you swap the definition of the word you are using.

If the individual is made up of many cell systems, evolution can indeed
be part of an individual as the individual cells within, say, a human
system have generations of their own within that individual.

>Changes
> in the gene pool of a population over time are reflected in the
> differential appearance of alterations in the characteristics and
> traits of individuals coming from that population at different points
> of time.

And you don't think the immune system cells are part of an immune
system gene pool? They are just as much as a coloney of bacteria is
part of a gene pool.

> Lymphocytes in the vertebrates do not play much of a
> role in the shifts to the gene pool. (It is possible that some of the
> features of the lymphocyte gene segments that are encoded in the
> genome can be selected for or against by pathogens, such as
> those producing "superantigens" might have on specific V-beta
> chains of the T-cell antigen receptor, so I said "not play much of
> a role" but since the actual antigen binding site for antibodies that
> B-cells produce or binding sites for the T-cell antigen receptor are
> not encoded in the genome, the specific binding sites are never
> passed on to offspring.)

The specific binding characteristics are passed on to the offspring of
the B- cells - from generation to generation of these immune-system
cells. Again, gametes do not have to be involved in order for real
Darwinian-style evolution to be taking place within your own body.

> Because these critical features come from
> outside of the genome (so to speak, created by VDJ joining) they
> have not been able to be usurped by pathogens the same way
> that many other immune system components have been.
>
> > Do antibodies undergo random changes that are preferentially
> > selectable, based on functional differences, over generations of immune
> > cells?
>
> While the point about "generations of immune cells" is moot (that
> the cell divides or not has little to do with this), B-cells do have
> somatic hypermutation that can increase the affinity of the binding
> site of the antibody in an immune response. That is *not* evolution.
>
> > How is this not a type of evolution?
>
> It is an evolution of an immune response. It is *not* evolution.

It *is* evolution.

>
> > A new function is realized
> > over time via random mutation and function-based selection - right?
>
> No. No "new" function is gained.

An alteration of an exising binding site that produces a functional
beneficial change is the evolution of a new and improved function that
was not there before. A new antigen is recognized to a greater and
greater extent.

Anyway, this is all I have time for today. I find it quite interesting,
in any case, that I'm the one arguing for evolution here and you
against it.

John Harshman

unread,

Aug 19, 2006, 12:56:03 PM8/19/06

Seanpit wrote:

You are confused. The reason your coin toss probabilities can be
multiplied to determine a joint probability is that the coin tosses are
independent. Independent event probabilities can be multiplied in this
way. Non-independent event probabilities can't. And that's what Norman
was demonstrating to you with his coin toss example. In any one toss,
the probability of getting heads is not independent of the probability
of getting tails. If you get heads, you can't get tails, and vice versa.
Is it possible that you don't know the meaning of "dependent" in
probability theory?

Perplexed in Peoria

unread,

Aug 19, 2006, 1:12:33 PM8/19/06

"Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1155980766....@m79g2000cwm.googlegroups.com...

> >You are
> > in the mode of multiplying small probabilities to get such a tiny
> > number that you can prove the final event to be impossible. That
> > argument has been shown repeatedly to be wrong because the events
> > involved are not independent so that the probabilities don't multiply.
>
> Interesting . . . Please do explain your notion of the statistics
> involved. Please do explain to me how events that are not independent
> (i.e., events that are *dependent* on each other) have a probability of
> occurrence that is not based on multiplying the probabilities of each
> individual event with each other?
>
> For example, what is the probability of flipping a quarter and landing
> it on heads 3 times in a row? Is it not 1/2 x 1/2 x 1/2 = 1/8?
>
> The events involved are not independent, that's true. They are

> dependent. ...

Sean, you are just dead wrong. Which surprises me because IIRC
you did pretty well the last time a probability question came up.

The events in three successive flips of a fair coin are _independent_.
That is why you can multiply the probabilities.

But now lets try flipping a bent quarter. The bending was done
'randomly' - there is no more reason to suspect that the bending
favors heads than tails. If you wish, you can imagine that it
was flipped and then picked up without looking before inserting
it into the bending device.

Now what is the probability of heads on the first flip. 1/2, I
think. But the probability of three heads is no longer 1/8.
The successive flips are not independent. They all depend on
the same datum - which way the coin is bent.

I recommend that you check out some educational resources on
probability theory, focusing on the definition of independence
and on the subject of conditional probabilities.

Von R. Smith

unread,

Aug 19, 2006, 1:56:25 PM8/19/06

All this verbiage, and you still didn't answer my question. What part
of: " I don't want another analogy. I want an actual description of
an actual difference in genetic sequence" did you not understand? Your
analogy is weak because there is no analog to the "abcdef" that you can
point to as a constraint on genetic sequence.

We have already dispensed with the notion that your "3D requirement"
for function imposes an actual requirement of sequence contiguity in
the genome. The genes coding for the flagellum in E. coli are spread
out over one million base-pairs of genome. The structural proteins of
the transport apparatus alone are coded for on operons more than 100
kbp apart. So there is no "abcdef" that distinguishes this function
with a "3D requirement" from functions that don't. In either case, the
genes coding for "abc" and "def" could be a large distance from one
another. In eukaryotes, there isn't even an "abcdef" analog within
individual genes.

So let's try this again: What actual constraints on genetic sequence
exist for a function with a "3D requirement" that don't exist for
genetic sequences coding for other types of functions, such as enzyme
cascades? How are these genetic sequences more specific? Once more:

hersheyhv

unread,

Aug 19, 2006, 2:11:45 PM8/19/06

Sorry Sean. But there are no little assembly fairies working in any
bacterial cell that takes the individual proteins and assemble them
into a flagella (or anything else that the cell makes). Often the
"spontaneous aggregation" requires that events occur in a time-ordered
fashion where each part only self-assembles after a previous step. Or,
in some cases, a chaparone protein is required for assembly, but these
proteins bind and interact with substrates by the same "spontaneous
aggregation" because of Brownian motion and the key-in-lock nature of
protein-protein interactions. So, ultimately, unless you have evidence
for little protein assembling intelligent fairies, the assembly of
*everything* in a cell is due to chemical interactions. Timing of
synthesis is sometimes important. Order of assembly is sometimes
important. But there are no assembly fairies. These structures
self-assemble because of their chemistry, not because the fingers of
assembly fairies are pushing them around.

> It is like
> expecting the parts of a watch, if all put into a paper bag and shaken
> for a few hours, to self-assemble into a functional watch. It just
> won't happen. The parts of a flagellum will not self-assemble outside
> of very specific tightly controlled production and manipulation of the
> parts at just the right time and place. Timing is everything for the
> "proper" assembly of the parts of a flagellum.

SFW? The parts still self-assemble. They are not assembled by any
intelligent agent.

> If you disagree, I'd be very interested in the basis for your argument
> here. Is it really your position that the proteins used for flagellar
> assembly would simply self-assemble properly if they were all put in
> the same general vicinity at the same time?

It really depends on the structure. Some complex multiprotein systems
(like ribosomes or microtubules) do, indeed, self-assemble when they
are put together in the right environment. The timing of synthesis or
assembly of parts is not due to any intelligent agent or homunculi
working in the cell. That sometimes involves self-assembly,
independently, of subparts of the total. For example, the motor of the
eubacterial flagella and the rotating whip self-assemble separately and
then the subparts come together.

> > >> > An
> > >> >individual protein does not necessarily fold itself properly. It has
> > >> >to be folded in the proper way after translation. It then has to be
> > >> >carried to the proper place and manipulated in the proper way into its
> > >> >proper position in the system that is being built.
> > >>
> > >> For the most part, no. In most proteins the 3D folding patern is
> > >> determined solely by the the sequence of the protein.
> > >
> > >Many proteins require other proteins to fold them properly. This is
> > >true of many of the proteins in the flagellar motility system. They
> > >simply do not fold, unfold, and refold properly by themselves.

Also irrelevant. Many times the chaparone is merely a modified version
of the protein that it aids in forming correctly. That sort of thing
is easy to evolve.

> > This is irrelevant to the overall concept. Not all proteins require
> > other proteins to fold. It is not known whether the original proteins
> > involved in the ancestral bacterial flagellum needed them. But even
> > so, that just means that a few more proteins are needed to produce the
> > complete assemblage.
>
> Not just a few more proteins, but a few more proteins as well as very
> specific timing of production and breakdown of proteins into and out of
> solution.

Again, all of these steps do not mean that the assembly of the
structure is anything but *self-assembly*. There are no little
homunculi assembling these structures. Only proteins. That the order
of assembly is not "all-at-once" doesn't make the assembly anything but
self-assembly. That some of the proteins require other proteins acting
as scaffolding to properly assemble doesn't make the assembly anything
but self-assembly based on innate chemical interactions of proteins.
There are no intelligent fairies in these cells constructing flagella.
Do you have some *real* point here?

Sometimes yes, sometimes no. Depends on particular environmental cues
and timing. But it still is *self* assembly and not *non-self*
assembly.

Describe exactly where this is the case in flagella. There are
certainly time points when the partially assembled whip structure will
only accept one protein and not another, but that is not a matter of
timing. It is a matter of a change in structure and accordingly
changed affinity. There can even be "counting" going on in some
structures (take up 20 copies of protein A, then switch to protein B).

SFW. There is extensive duplication in the flagellar proteins. There
is clear evidence that many of the proteins arose for other functions.
You are simply assuming that all 30,000 bp came from some random
sequence of DNA. It clearly did not. If you had *any* evidence that
the flagella arose by starting from a random sequence and randomly
wandering through total sequence space to reach the current sequence,
you might have a point. But since evolution does not work by this
mechanism, you don't. The number 30,000 bp only has meaning wrt a
strawman version of evolution working by a mechanism we can all agree
did not happen. So when are you going to present an argument against
the *real* theory of evolution rather than this bogus strawman? When
are you going to tell us which of these bp *necessarily* had to arise
by a random walk from some random sequence with no intermediate
utility?

You seem to be applying a strange _ex post facto_ analysis: Determine
a currently observed sequence of cards you are dealt and then use the
probability of drawing that hand as *evidence* that you could not
possibly draw that hand. That is bogus statistics even *if* evolution
worked like a random deal from a deck. The probability of being dealt
the hand you actually have is 1.

hersheyhv

unread,

Aug 19, 2006, 2:25:33 PM8/19/06

Seanpit wrote:
> Marc wrote:
>
> > Here is the thing, Sean - you insist that *something* must be making
> > bits of new genetic material beyond a certain size of fragment that you
> > think is an upper limit, and you insist that gene duplication can only
> > make something that is already there and so there *must* be a designer
> > working to make those bigger things, right?
>
> No. That's not what I'm saying at all. I'm not just talking about
> making bits of just any kind of new genetic material. I'm talking
> about making new genetic material that also results in a novel system
> of function that requires more than a few thousand bases at minimum in
> order to work. Gene duplication can produce a whole lot of extra
> genetic material. That's not the problem. The problem is that gene
> duplication cannot produce extra genetic material that also has the
> ability to provide a new genetic function to the organism beyond
> extremely low levels of functional complexity.
>
> It's like copying a whole page of material out of a book, with a few
> extra mutations, and getting another 3-letter word out of the deal. It
> is easily to get the equivalent of 3-letter word functions by such
> methods. It is another thing entirely to get a new function that
> requires an entire page or several pages, at minimum, to code for it.
> Gene duplication just doesn't do that for you. It just gives you more
> of what you already have. It doesn't produce novel functions or
> provide added means of producing novel functions beyond very low levels
> of functional complexity.
>
> > So what if you are just a
> > little bit wrong about the outcome of gene duplication?
>
> Then I'd be wrong . . . Obviously! Where is your evidence beyond your
> just so stories about sequence homologies? Where are your *observable*
> demonstrations of the evolution of novel *functions*.
>
> So far, all you've given me as far as observable evidence are sequence
> homologies, gene duplications, and the transfer of viral DNA to the
> Koala genome. None of these qualify as even a single observation of
> the evolution of a new function that wasn't already there.
>
> > What if, as is
> > now accepted in science, duplication and divergence is a major force
> > in the development of new functions?
>
> I have no problem with gene duplication and divergence. What I do have
> a problem with is your notion that gene duplication and divergence
> actually give rise to new functions - new functions that require a
> minimum of more than a few thousand fairly specified bp of DNA.
>
> > It sort of weakens the need for
> > your "designer", right?
>
> Not unless you can show or reasonably explain how gene duplication and
> divergence via any kind of random mutation could ever produce a new
> functional system that requires more than a few thousand fairly
> specified bp of DNA - DNA that produces a protein-based system of
> function where more than 1,000 or so residues all work together in a
> fairly specified order relative to each other.
>
> Now, don't come back like Von Smith has often tried to do with some
> sort of cascading system. Cascading systems of function have very low

> overall specificity requirements, relatively speaking. A system that
> uses an equivalent minimum number of residues with the additional
> requirement of having each of the protein parts in specific arrangement
> relative to each other is far more specified and therefore "rare" as
> far as its likelihood within sequence space or appearance within a
> given genome via random walk (via random mutations) of any kind.
>

> > This post is a copy of your reply to me in a different thread, right?
>
> Yep . . .
>
> > You have a statement top-posted above that would be slightly
> > different from the other reply (i.e. it is lacking), but the fact that
> > you have copied your entire reply here from another thread (instead
> > of just answering my question with an original reply) is analogous
> > to a genetic duplication event.
>
> That's true!
>
> > Nice one, Sean!
>
> Thanks!
>
> > Already my reply
> > in this thread is different to the comments that I will be making to
> > the original version of this message in the other thread. Here, I am
> > considering how this very message serves as an illustration of how
> > divergence of duplicated material works, while back in the original
> > message I will most likely reply about how you should go back and
> > read my comments on the basis of the immune system a bit more
> > carefully since I still think you fail to grasp them.
>
> I grasp them just fine. Your comments and insights into the immune
> system and its supposed evolution really weren't "all that" . . .
>
> > (Of course, not
> > making a reply to that thread is also a quite valid example of how
> > evolution functions with respect to duplicated material. If the gene
> > has a quite essential role, then one of the copies needs to maintain
> > that function.)
>
> Of course. You have one copy to maintain a previous function and a new
> copy that can explore sequence space via random mutations of some kind.
> This still doesn't answer the problem of actually finding a novel
> sequences with an attacked beneficial function beyond extremely low
> levels of functional complexity . . .

Ever hear of chimeric duplication? But at what point does simple
divergence produce a "new" function? How does one recognize that a
sequence is producing a "new" function rather than merely using
different substrates, producing different products, or having altered
properties, or being used for a different function (such as eye
crystallins) entirely? What is the difference between an isozyme and
new gene?

> > > thousand fairly specified bases of DNA.
> >

> > You again overlook the other driving force in evolution, gene
> > duplication, that answers your conundrum quite clearly.
>
> How did I overlook gene duplication? I discussed gene duplication in
> this very post, you just snipped that part of my discussion. Where
> have you even attempted to explain how your duplicated gene(s) help in
> any significant way in the finding of a novel beneficial functional
> system?

Ever hear of chimeric duplication?
>
> > Perhaps you might want to
> > read the Annual Review Biochem. paper I cited (which you don't seem
> > to have looked at yet), or the paper that John pointed out recently:
> > "Allelic divergence precedes and promotes gene duplication"
> > Evolution Int J Org Evolution. 2006 May;60(5):881-92. PMID: 16817530
>
> Why don't you explain to me, in your own words if you like or using the
> words of the authors of these papers you've listed here, just how gene
> duplication helps evolutionary mechanisms find novel systems of
> function beyond very low levels of functional complexity?
>
> You seem to be very good at providing irrelevant references. If you
> disagree, thinking that these references support your position in any
> significant way, then please do explain your own argument here, for
> yourself. You can quote any reference you like, but please do actually
> present an argument of some kind. Saying over and over again that
> "gene duplication solves the problem" isn't helpful. Please do explain
> how gene duplication solves the problem. How do these duplicated
> portions of DNA find new beneficial functional systems that require
> more than a few thousand fairly specified bp of DNA?
>
> > Try these as well:
> > "Protein family expansions and biological complexity"
> > PLoS Comput Biol. 2006 May;2(5):e48. Epub 2006 May 26.
> > PMID: 16733546
> > http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=16733546
> >
> > "Widespread genome duplications throughout the history of
> > flowering plants" Genome Res. 2006 Jun;16(6):738-49.
> > PMID: 16702410
> >
> > "Gene duplication and functional divergence of the zebrafish
> > insulin-like growth factor 1 receptors."
> > FASEB J. 2006 Jun;20(8):1230-2. Epub 2006 May 16.
> > PMID: 16705083
> >
> > "Combinatorial RNA interference in C. elegans reveals that
> > redundancy between gene duplicates can be maintained for
> > more than 80 million years of evolution."
> > Genome Biol. 2006 Aug 2;7(8):R69 [Epub ahead of print]
> > PMID: 16884526
> >
> > "Frequent appearance of novel protein-coding sequences
> > by frameshift translation"
> > Genomics. 2006 Aug 3; [Epub ahead of print]
> > PMID: 16890400
> >
> > (This last report seems quite interesting - I'd like to hear
> > your thoughts about this one after you read it, Sean.)
>
> Frameshift translation does produce novel protein sequences, sometimes
> with novel even beneficial functions. The problem is that the functions
> produces by such frameshift mutations never require more than a few
> hundred fairly specified residues at minimum in order to work to a
> minimum selectable level.
>
> For example, the nylonase function has arisen via such a frameshift
> mutation in certain bacteria. That is real observable evolution in
> action. This novel beneficial function arose via random mutation and
> function-based selection. Great! Evolution is a fact! Sure it is.
> It is a fact at very low levels of functional complexity. The nylonase
> function doesn't require more than a couple hundred fairly specified
> residues at minimum. It isn't a very complex function at all. The
> nylonase function can be produced by a relatively small loosely
> specified single protein enzyme. See the problem?
>
> < snip >
>
> > >You started talking about
> > > changes in the pathogen, antigen changes, and the need for an immune
> > > system that can compensate for these changes.
> >
> > Not exactly. The immune response in an individual is more or less
> > completely unique, even in twins I would dare say, and it is this
> > evolutionary system, going back some 450 million years, that used
> > this right from the start - it's one of the very reasons that
> > vertebrates
> > were able to evolve so well, by a system of self-recognition and the
> > ability to respond to non-self and altered-self which evolved alongside
> > the established innate immune system. Each individual has their
> > strengths and weaknesses in their immune repertoires, but that is
> > *NOT EVOLUTION*, it is the result of a system that did evolve but
> > the immune response in an individual does *NOT* itself contribute
> > to downstream evolution (except in the general sense that some
> > components like an given MHC allele or variation in a cytokine or
> > receptor can be selected for or against) since the antibody binding
> > sites and the TcR binding sites are *NOT* in the germline.

>
> Germline evolution isn't the only type of evolution out there.
> Improvements in immune system specificity for a given foreign antigen
> most certainly count as real evolution in my book. Just because it
> isn't germline evolution doesn't mean it isn't evolution - improved
> function via random mutation and function-based selection. That's
> exactly what it is. It doesn't have to be passed on to the offpring of
> the animal with the immune system in order to be "evolution" - passed
> on to generations of immune system cells within the same creature.
> That's right, "generations" of somatic cells are produced in the same
> creature and the functions of these cells can "evolve" over time. It's
> still evolution regardless of the fact that it isn't germline.
>

> > > Of course an entirely
> > > new system doesn't need to evolve to detect such antigen changes! If
> > > you are talking about the evolution of the immune system, then no, I
> > > don't believe that the immune system evolved from ancestor creatures
> > > that didn't have an immune system. The minimum coding requirement for
> > > a useful immune system is far too complex for evolutionary mechanisms
> > > to achieve even in trillions upon trillions of years of time.
> >
> > Oh, Sean - quit the "trillions of years" stuff. Using such excess of
> > scale is trite and shows no appreciation for deep time. A thousand
> > million years is an extraordinary long time and there is no need to
> > make it sound otherwise.
>
> You don't seem to understand the enormity of the statistics involved
> here. A thousand million years is a drop in the proverbial bucket in
> comparison to the time that would be needed to evolve across a
> non-beneficial gap of only a few dozen fairly specified residue
> differences.
>
> > My six year old has a better respect for the
> > scale of numbers than that. (He is actually *very* good with numbers,
> > perhaps partly from the number of x-box game scores that go up
> > into millions and such that he has seen and can grasp quite well.)
> > Your use of "trillions" is stupid.
>
> Well, perhaps you can get your six-year-old to help you with the
> concept of trillions? - that the answer to some problems does indeed
> require much larger numbers than mere billions? You need to expand
> your understanding of the true enormity of the gaps involved here Marc.
> Even trillions of years are a drop in the bucket. Trillions to the
> power of trillions of years don't even do it.
>
> > ......... snp the rest here .....
> > (This now becomes a protein domain doing an exon shuffle in the
> > duplicated-message/thread model of gene duplication in evolution)
>
> And exon shuffle that ends up producing what? - again?

z

unread,

Aug 21, 2006, 12:46:18 AM8/21/06

On 15 Aug 2006 07:52:32 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

>
>z wrote:
>
>> >Take a system that requires specific orientation of all of its parts
>> >relative to each other. The production of such a system is quite
>> >unique in sequence space. The parts involved could have been arranged
>> >in any myriad number of ways. The fact that they are arranged in such
>> >a way as to produce a specific setup with a specific function requires
>> >a great deal of collective constraint on the system as a whole.
>>
>> In essence, word salad. If we want to limit the discussion to
>> protein-protein interactions all we need brownian motion.
>
>Not true . . . Brownian motion isn't enough to assemble the parts of a
>flagellar motility system even if all the parts are there at the same
>time.

For the flagella, no. You woul'nt be able to keep all the parts in
solution- transmembrane proteins don't behave in aqueous solution.
You can polymerize the flagellar subunits by themselves, howver.

>
>> > An
>> >individual protein does not necessarily fold itself properly. It has
>> >to be folded in the proper way after translation. It then has to be
>> >carried to the proper place and manipulated in the proper way into its
>> >proper position in the system that is being built.
>>
>> For the most part, no. In most proteins the 3D folding patern is
>> determined solely by the the sequence of the protein.
>
>Many proteins require other proteins to fold them properly. This is
>true of many of the proteins in the flagellar motility system. They
>simply do not fold, unfold, and refold properly by themselves.
>
>> >extraordinarily fine-tuned timing. Such timing is only achieved with
>> >the use of very finely orchestrated production of protein parts in just
>> >the right place and time. Of course, this requires very specific
>> >arrangement of the codes in the underlying DNA. You just can't shift
>> >the codes around and have the system self-assemble properly. The
>> >underlying codes must be specifically arranged relative to all the
>> >other codes for all the other sequences involved.
>>
>> Again, word salad. What codes are you talking about? The proteins of
>> the flagella (for example) self assemble. There is no DNA code post
>> translation.
>
>You are again mistaken. The proteins of the flagella do not
>self-assemble properly into a flagellar motility system if they are
>simply put in the same place at the same time. The specific order of
>their formation is vital to the assembly process.

What are talking about? It's a relatively simple system as far as
genetic controls go, at least in E. coli. If there is a need for
flagella, the transcription factors FlhC and D are made. These turn
on the genes that make the type III secretion system hook-basal body,
sigma-28 and the the sigma-28 antagonist FlgM.

This is not a gene by gene, protein by protein cascade. If cell
senses a need for flagellar motility, it starts by making the
transcription factors to make the protein pump, hook, and basal
portion of the motor all at once! The proteins self-assemble into the
basal body-hook complex all by themselves (obviously they need
ribosomes and some other factors for there own sysnthesis). When the
hook is completed, this allows for the export of FLgM, allowing
sigma-28 to turn on the genes for the flagella itself, as well as the
rest of the motor. Again, all at the same time and again
self-assembling.

So, your specified order is as complex as 1) Start making flagella, 2)
Make the base and secretory parts, 3) Make the flagella and finish the
motor.

At each stage, there substructures formed in a defined sequence.
Again, this is not a regulatory mechanism. All the parts are there for
each stage and the self-assembly proceeds via defined intermediates.
Parts A and B self assemble, and C hangs out untill it can bind to the
A-B subassembly etc.

>
>> >This is different from the codes for a cascading enzymatic system. The
>> >final product for such a system does not require specific orientation
>> >of each of the enzymes with all the other enzymes. This difference is
>> >not described by a factorial. It is an exponential difference.
>>
>> Cascading enzyme systems are coded for linearlly. Orientation of
>> enzymes is pretty much irrelevant for the the vast majority of
>> biology. Your point was?
>
>That's my point. Orientation of enzymes in an enzymatic cascade,
>relative to the other enzymes in the cascade, is not require for the
>function of the cascade to work. This is not true of the systems like
>the flagellar motility system where all the individual parts do require
>orientation relative to all the other parts.

You miss the point. There is a huge amount of structural information
required to "specify" an enzymatic cascade. The active site of each
enzyme must recognize both the substrate and the product of the
reaction.

Sequence space doesnt look at protein-protein interaction. It merely
is a description of the sequence of a protein and its neighbors.

We have looked at a large number of crystal stuctures of a particular
class of proteins that have natuarlly evolved to bind to a particular
surface on a particular protein with exquisite specificity. Us
biology types like to call thses evolved proteins antibodies.

Your body can in a span of a few weeks produce an antibody to almost
any foreign protein. Real time protein evolution in that the
resulting antibody will contain sequences that are different from
anything in your germ line.

Protein-protein interactions are easy to evolve. While ther are
examples of proteins that actually swap bits of secondary structure to
form quaternary structure, for the most part it's just two surfaces
sticking together. You fixate on this as if it's a big deal-
something that caused me to scratch my head and wonder why. Getting a
protein to recognize a small moleule and actually do something with it
is far trickier.

>
>> We have fairly large datasets now. It's very clear that there are a
>> smallish numeber (say ~100) of protein folds that are found commonly
>> in biological systems. And its quite clear that they can be very
>> divergent in sequence and still have the same 3D structure.
>
>That's also true. However, when it comes to higher and higher levels
>of minimum system requirements the non-beneficial ways in which these
>"smallish" number of folds can be arranged relative to each other
>increases exponentially faster than the very small number of ways that
>will actually work to perform a given function - like flagellar
>motility.

Expectations are everything. If you expect that you can get a fully
functionally flagellar motility system all in one go, sure you'd be
disappointed. The cooption of other prexisiting simpler systems has
been presented and ignored by you so I won't elaborate further.

Again, expectations. Evolutionary theory does not predict that a
flagellar motiltiy system just up and put itself together all at once
due to one organism experiencing one selective event.

Think modular, and think cooption.

>
>> >> That proportion *may or may not* be lower (and
>> >> hence the specificity higher) for proteins requiring a particular "3D
>> >> order" than it is for proteins that produce a particular enzyme
>> >> activity.
>> >
>> >You're wrong. Systems that require a specific 3D order require a much
>> >greater underlying specificity of code than do systems that do not
>> >require specific 3D order of all of their collective parts.
>>
>> Perhaps they do if they require an engineering diagram, but not if
>> they self-assemble. And, as all biology they do so in messy an
>> ineffcient ways.
>
>You're quite mistaken. Such higher-level systems of function, like the
>flagellar motility system, do not simply self-assemble even if all the
>needed parts are put together in the same place at the same time.

The flagella does, albeit in two seperate steps. All the parts for
the basal body-hook are made at once. All the rest are made at once
once the hook is complete. It self assembles.

>It is like doing a chemistry experiment. If you don't add and remove the
>chemicals in the proper way at the proper time, your experiment will
>fail. The same thing is true when it comes to building a multiprotein
>system of function in a living thing. The parts simple do not
>self-assemble outside of proper finely tuned timing.

You don't understand flagellar assembley as well as you think you do.
You are confusing an order dependant self-assemebly with one that is a
just-in-time synthesis and assembly one.

>
>> >> Which one actually has more specificity is an issue of fact,
>> >> not something you get to decide a priori and then use to rationalize
>> >> redefining your terms mid-argument.
>> >
>> >That's right. The specificity of a system can be determined quite
>> >consistently by looking at the specific 3D requirements of that system.
>> >I really don't see how you can manage to make this relatively simple
>> >concept so obscure in your own mind.
>>
>> What a horrible conceit.
>
>What deliberate blindness . . .

Your claim is that you can look at the 3D requirements of a biological
system AND determine that it is designed. That's a conceit by
definition. For your favorite (only?) example, we only have atomic
level detail on a few flagellar proteins. The rest of the 3D
structure is at the cryo-EM level. We can assign locations to
proteins roughly within that, but not exact loactions for the most
part. And yet you can say that your analysis of sequences and
structure lead you to the conclusion of an invisible designer.

What you are saying is "What I assume about 3D structure of proteins
means that they must be designed". You have no evidence. That's
conceit.

The rest of us who actually work with the damn things can only explain
what we find by "descent with modification". Or look for an
incredibly tiny pixie, but you can drink past THAT stage.

Oh, and did your designer leave any other "traces" besides the
bacterial flagella? It seems to the only specified example you toss
out.

B Miller

z

unread,

Aug 21, 2006, 1:15:13 AM8/21/06

On 19 Aug 2006 09:36:55 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

Well of course if you don't accept that organsims that are related by
sequence are also related by descent, then you cannot accept Marc's
(and the rest of biology) assumption. You also cannot accept
paternity tests either. Your designer could do whatever it wants.

>
>In this particular discussion, you can't use as evidence what we
>already both accept as fact. What you have to do is show evidence that
>your proposed mechanism, random mutation and natural selection, is in
>fact capable of producing higher-level functional systems. Papers that
>do not deal with this actual mechanism, choosing instead to rely only
>on the assumption that sequence similarities mean common descent, just
>don't support your argument in this case.

Are you related to your biological parents in a way that is can be
verified by DNA sequencing? If not, you win. If so, then Marc's
assertiaon stands. Obviouslly, at some point in the past the
relationships will get murkier and more arbitrary- am I your 45th of
3785th cousin?

>
>What you need to do is explain how gene duplication or any other kind
>of genetic rearrangement/mutation can possibly produce new functions
>that require more than a few thousand fairly specified bases of DNA.
>You have yet to do this. You seem to think it enough to just wave your
>hand and declare than gene duplications solve all problems. How Marc?
>How do gene duplications help to create higher-level functional
>systems?

Lampreys and hagfish have a single alphaglobin gene, one that does not
exhibit all the fun biochemistry that an alpha-betaglobin heteromer
does. Bohr effect and 2,3 DPG binding.

>
>Now, don't come back and list a bunch of references. Explain it to me
>in your own words. You can use references to help you, but I want to
>see if you understand what you claim to understand. Please do explain
>exactly how gene duplication helps evolution find higher level
>functional systems in the potential of sequence space.

Sequence space is just that- there is no function in sequence space.

>
>> > Why do you keep talking about gene duplication like I don't accept it?
>>
>> Because your "accepting" of it is flawed.
>
>How so? I accept that it happens just fine. I just don't accept that
>it produces new higher-level functions. You have yet to show otherwise
>beyond your just-so stories and appeals to sequence similarities.

Gee, a reconstruction of ancestral protein and a description (with
experimental testing) of the possible trajectories to the modern state
don't count?

>
>> > As I've told you over and over again, I have no problem with gene
>> > duplication - or even genome duplication. What I have a problem with
>> > is the notion that gene duplication somehow makes it easy for evolution
>> > to find novel systems of function beyond very low levels of functional
>> > complexity.
>>
>> See? That's where your flaw comes in. Put duplication together
>> with exon shuffling and you have a great deal of new function.
>
>Oh yeah? How Marc? Any observable examples of this beyond very low
>levels of minimum size and specificity requirements?
>
>> Please tell me that you have considered reading the paper
>> from the 2005 Annu. Rev. Biochem. - I say considered because
>> you clearly haven't actually read it, have you?
>
>Provide your own explanation here Marc. You can use this or whatever
>other paper you want to help you. However, simply listing off a bunch
>of references is not the same thing as making a good argument of your
>own.

You have yet to gogently describe your point. You misdescribe
sequence space, you don't seem beleive that organisms can be related
by DNA in a reliable fashion, and you assume that complex fucnctions
happen all at once. Give me a prediction. An experiment that should
be yes/no, or an experimental finding that says "aha!" to you.

>
>> > As far as I can tell, this notion of yours is simply an unsupported and
>> > statistically untenable assertion - a "just so story" at best.
>>
>> It isn't *my* notion, Dr. Pitman, it is the accepted scientific view.
>
>I realize that. It is also your own individual notion. If you really
>do understand the basis of this generally accepted notion, then please
>do provide an actual explanation of your own. Don't just appeal to
>someone else or some other paper. Please do provide your own argument
>here.

Well, if we all call them dogs, tell us why they should actually be
called peonies.

>
>> > These
>> > stories are based on absolutely nothing more than the notion that
>> > sequence similarities necessitate common descent via random mutation
>> > and natural selection. This notion just isn't valid without a
>> > reasonable mechanism. The ToE doesn't have one. Gene duplication isn't
>> > the magic bullet. It just makes more of what is already there. It may
>> > free up the extra copy to undergo a bit of random walk/sampling within
>> > sequence space, but this just isn't going to do much as far as finding
>> > new functions at even moderately higher levels of minimum size and
>> > specificity requirements this side of a practical eternity of time.
>>
>> Can you provide a citation that supports your position here?
>
>Of course not because this isn't the mainstream view. It is my own
>view. If you really think the mainstream view is correct, please
>explain to me in your own words how evolution can produce higher-level
>functions with the use of any sort of random genome manipulation
>combined with natural selection. Spell it out Marc. How does gene
>duplication and exon shuffling end up producing new functions at higher
>minimum size and specificity requirements?

Puzzle this one then. Humans have rougly 20,000 genes and can produce
over 100,000 different proteins due (in part) to alternate splicing.

B Miller

Seanpit

unread,

Aug 21, 2006, 2:19:29 PM8/21/06

z wrote:

> >> Others might say that these papers describe observations of such
> >> evolution quite clearly. There is a great deal of value in the
> >> sequence data. (Which is why it is such a threat to your way of thinking,
> >> right?)
> >
> >This discussion isn't over the notion that there are indeed sequence
> >similarities between different high-level functions. I already know
> >that. Telling me to read dozens of papers that demonstrate this isn't
> >going to show me anything that I don't already know.
> >
> >The question at hand, in case you haven't figured it out yet, concerns
> >the notion that sequence similarities necessitate common evolutionary
> >ancestry. That's what the discussion is about Marc. You say that
> >these similarities are best explained by common descent while I say
> >that they are best explained by common design when they go beyond very
> >low levels of functional complexity.
>
> Well of course if you don't accept that organsims that are related by
> sequence are also related by descent, then you cannot accept Marc's
> (and the rest of biology) assumption. You also cannot accept
> paternity tests either. Your designer could do whatever it wants.

Paternity testing is based on a well-understood mechanism of random
mutations that are largely non-functional/neutral. This is easily
explained. The mechanism for non-functional differences is well
established. The problem is that the evolutionary mechanism for
functional differences beyond very low levels of functional complexity
is not at all established.

You do understand the difference between functional and non-functional
genetic differences - right?

> >In this particular discussion, you can't use as evidence what we
> >already both accept as fact. What you have to do is show evidence that
> >your proposed mechanism, random mutation and natural selection, is in
> >fact capable of producing higher-level functional systems. Papers that
> >do not deal with this actual mechanism, choosing instead to rely only
> >on the assumption that sequence similarities mean common descent, just
> >don't support your argument in this case.
>
> Are you related to your biological parents in a way that is can be
> verified by DNA sequencing?

Yes! However, these differences are largely non-functional/neutral
differences. You do understand this? - don't you?

> If not, you win. If so, then Marc's
> assertiaon stands. Obviouslly, at some point in the past the
> relationships will get murkier and more arbitrary- am I your 45th of
> 3785th cousin?

We aren't talking about just any kind of genetic differences here. We
are talking about differences that are not only different in sequence,
but in function. Beyond this, we are talking about different
functional systems that have a minimum requirement of more than a few
thousand fairly specified bp of DNA.

You can't simply appeal to any sort of genetic difference here. We are
specifically interested in functional differences at higher levels of
functional complexity. There just aren't any examples of the evolution
of even one new system of function beyond very very low levels of
functional complexity.

> >What you need to do is explain how gene duplication or any other kind

> >of genetic rearrangement/mutation can possibly produce new functions
> >that require more than a few thousand fairly specified bases of DNA.
> >You have yet to do this. You seem to think it enough to just wave your
> >hand and declare than gene duplications solve all problems. How Marc?
> >How do gene duplications help to create higher-level functional
> >systems?
>
> Lampreys and hagfish have a single alphaglobin gene, one that does not
> exhibit all the fun biochemistry that an alpha-betaglobin heteromer
> does. Bohr effect and 2,3 DPG binding.
> >
> >Now, don't come back and list a bunch of references. Explain it to me
> >in your own words. You can use references to help you, but I want to
> >see if you understand what you claim to understand. Please do explain
> >exactly how gene duplication helps evolution find higher level
> >functional systems in the potential of sequence space.
>
> Sequence space is just that- there is no function in sequence space.

Not true. Sequence space contains all the possible sequences - to
include those that would be beneficial if they were ever found by a
given genome in a given environment.

> >> > Why do you keep talking about gene duplication like I don't accept it?
> >>
> >> Because your "accepting" of it is flawed.
> >
> >How so? I accept that it happens just fine. I just don't accept that
> >it produces new higher-level functions. You have yet to show otherwise
> >beyond your just-so stories and appeals to sequence similarities.
>
> Gee, a reconstruction of ancestral protein and a description (with
> experimental testing) of the possible trajectories to the modern state
> don't count?

Not if they don't involve a step-by-step discussion of how a new higher
level system of function could have come about via random mutation and
function-based selection and the odds that such mutations would be
realized in a certain span of time.

Behe was right in pointing out that no such papers exist - papers that
really get into the details of the statistics required to cross the
non-beneficial gaps between what is and what might be beneficially
functional if it could ever be found.

< snip rest >

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 2:30:57 PM8/21/06

Of course the probability of getting heads is not independent of the
probability of getting tails. However, getting a specific sequence is
dependent upon the order of appearance of heads or tails of each throw
relative to the other throws.

This is what the discussion is about - the odds of getting a specific
sequences of variables. Norm seems to be suggesting that I'm mistaken
in multiplying the odds of realizing a specific variable at each
position for a certain number of positions. He seems to be claiming
that this is not how the odds are calculated. If this is not what he
is talking about, I fail to see the relevance of the statement that
flipping heads is not independent of the odds of flipping tails. I
never said otherwise.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 2:35:36 PM8/21/06

Perplexed in Peoria wrote:
> "Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1155980766....@m79g2000cwm.googlegroups.com...
> > >You are
> > > in the mode of multiplying small probabilities to get such a tiny
> > > number that you can prove the final event to be impossible. That
> > > argument has been shown repeatedly to be wrong because the events
> > > involved are not independent so that the probabilities don't multiply.
> >
> > Interesting . . . Please do explain your notion of the statistics
> > involved. Please do explain to me how events that are not independent
> > (i.e., events that are *dependent* on each other) have a probability of
> > occurrence that is not based on multiplying the probabilities of each
> > individual event with each other?
> >
> > For example, what is the probability of flipping a quarter and landing
> > it on heads 3 times in a row? Is it not 1/2 x 1/2 x 1/2 = 1/8?
> >
> > The events involved are not independent, that's true. They are
> > dependent. ...
>
> Sean, you are just dead wrong. Which surprises me because IIRC
> you did pretty well the last time a probability question came up.
>
> The events in three successive flips of a fair coin are _independent_.
> That is why you can multiply the probabilities.

The individual events are indeed independent events. However,
realizing a specific *sequence* of variables is *dependent* upon the
specific order in which the variables are realized. That's clearly
been my whole position this entire time. I'm talking about the odds
that a specific sequence will exist in a given genome. Those odds are
calculated by multiplying the number of potential variables per
position by the number of positions in the sequence in question - as in
1 in 20^100 for a specific 100-character residue sequence.

Seanpit

unread,

Aug 21, 2006, 4:21:53 PM8/21/06

This isn't really an analogy Von. Exactly the same thing is going on
with protein sequences. The sequence abcdef is equivalent to a protein
made up of 6 specific residues arranged in a specific order. There
would only be one such residue sequence in the sequence space of 20^6
six-residue sequences.

Coding for such a specific residue sequence with the use of an
underlying DNA sequence would require just as much specificity in the
underlying DNA. The underlying DNA code could code for any one of the
20^6 sequences. Getting it to produce a specific residue sequence out
of all those possibilities requires an equivalent degree of
specificity.

If you think this is not true, what basis do you have for such a
notion?

> We have already dispensed with the notion that your "3D requirement"
> for function imposes an actual requirement of sequence contiguity in
> the genome.

We have? The 3D requirement is still what must be coded for by the
underlying DNA. Since there are many different possible 3D outcomes
given the same protein sequence for certain proteins, the underlying
DNA must be able to end up coding for the right 3D requirement with the
use of chaperone proteins etc. In the end, it is still the specific
final product that must be produced in order for the function in
question to be realized.

> The genes coding for the flagellum in E. coli are spread
> out over one million base-pairs of genome. The structural proteins of
> the transport apparatus alone are coded for on operons more than 100
> kbp apart. So there is no "abcdef" that distinguishes this function
> with a "3D requirement" from functions that don't. In either case, the
> genes coding for "abc" and "def" could be a large distance from one
> another. In eukaryotes, there isn't even an "abcdef" analog within
> individual genes.

Sure there is because the intron segments are spliced out in very
specific ways in order to make the abdef analog. Again, the final
product is the important target here. The DNA specificity cannot be
less than the specificity required by the final product. You can't
have the DNA option of coding for just any 6-character residue
sequence. You must have the DNA be able to code for one specific
6-character sequence. How is this done if the DNA itself isn't just as
specified as the final product? Any other specific 6-character
sequence could be coded for. The fact that one is coded for requires an
equivalent degree of specificity.

> So let's try this again: What actual constraints on genetic sequence
> exist for a function with a "3D requirement" that don't exist for
> genetic sequences coding for other types of functions, such as enzyme
> cascades? How are these genetic sequences more specific? Once more:
> I don't want another analogy. I want an actual description of an
> actual difference in genetic sequence.

Why don't you tell me how it would be possible to code for a specific
6-residue sequence without the underlying DNA sequence being just as
specified. You can use an analogy if that helps you.

Yes or no, couldn't the underlying DNA sequence code for any one of
20^6 sequences in 6-residue sequence space? How would the DNA be able
to hit upon just one of them in particular? Please do explain your
position?

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 4:45:39 PM8/21/06

I don't have the time to write out separate replies for the same
comments you make in different threads or posts within the same thread.

> I have some *very* high hopes that your passage above which
> I have flagged for the next chez watt will make it to the podium.

Me too! ; )

> It would be quite rewarding to have such a blatant, classic type
> of misunderstanding of evolution archived on the Chez Watt page
> for all time to come. I really hope that between us, you pull in
> enough votes to win next month. (Lurkers - I offer beers to those
> who will remember to vote for Dr. Pitman's passage on the many
> forms of evolution...

I gladly second this offer . . . I'm truly amazed that you can argue,
with a straight face, that only changes that are passed down via
gametes count as real evolutionary changes. Single cells reproduce in
a clonal fashion just like bacteria. Just because a bacterial colony
may get completely wiped out does not mean that the novel functions
that were evolved before extinction really weren't the result of
Darwinian-style evolution. That's ridiculous -right? In the same way,
how can you say that novel as well as functional changes in cellular
populations don't count as real evolution? What if a somatic cell line
happened to evolve a flagellar system that was actually useful to the
overall creature's survival and even reproductive fitness? Even though
this trait wouldn't be passed on to the offspring of that creature - it
wouldn't mean that this new beneficial function wasn't really the
result of real evolution in action. It still arose via random mutation
and function-based selection - just in a clonally producing somatic
cell line instead of a gamete cell line. Either way, it still seems to
me to be real evolution in action.

Don't you get it? I'm trying to give your position every possible
benefit here. I will concede my position if you can show an example of
a novel system of function arising via random mutation and
function-based selection anywhere, gamete transfered or not, biosystem
or computer system, beyond very low levels of functional complexity.
You should be taking advantage of this. I'd be much less suprised if I
said that evolution of somatic cells doesn't count because the evolved
functions die out with the death of the overall organism. You could
come back and say that's just a copout - and I'd agree with you. So,
wherever and however a functional system evolves, regardless of if it
can be transfered to offspring or not, that would count as an example
of evolution of a new function in my book.

I'm just trying to give you more options here and you keep trying to
shoot yourself in the foot?

> I would offer massages but nasht0n would
> have to give me a refresher course first, and I'm still waiting for
> him to read the PLoS-Biology paper on signs of selection in
> the human genome).
>
> (signed) marc

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 4:57:16 PM8/21/06

Ok . . .

> Event A: get heads on top.
> Pr { A } = 1/2.

Right . . .

> Event B: get tails on bottom.
> Pr { B } = 1/2.

Ok . . .

> Event C: get heads on bottom.
> Pr { C } = 1/2.

Right . . .

> A , B, and C are NOT independent events. Therefore
> Pr { A and B } is NOT Pr { A } x Pr { B }
> Pr { A and C } is NOT Pr { A] x Pr { C }

What is the probability of getting heads on the top 3 times in a row?
That's the question here Norm . . .

We are talking about specific sequences of variables here. What are
the odds that a specific sequence of variables will be realized? In
other words, what are the odds that you will flip a coin 10 times and
realize the specific sequence: HTTTHHHTTT?

Or, to put it another way, what are the odds that a string of residues
10-characters long, with 20 possible residues per position, will be one
specific residue sequence?

Or, what are the odds that the specific sequence AABBCCDDEE will be
picked out of a randomly generated pool of 10-character sequences (26
possibilities per position)?

Sean Pitman
www.DetectingDesign.com

John Harshman

unread,

Aug 21, 2006, 5:21:28 PM8/21/06

Seanpit wrote:

You seem not to understand the meaning of "independent", because you
claim that the joint probability of a series of dependent events can be
calculated by multiplying their individual probabilities. But this is
true only for a series of independent events. That's what the argument
is about. Norman was just trying to show the fallacy of your claim in a
way that even you would understand easily. But you seem unwilling to
apply that understanding to the general case. But here is the lesson
again: probabilities can be multiplied only if they are independent. Did
you get it that time?

Perplexed in Peoria

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Aug 21, 2006, 5:22:34 PM8/21/06

"Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1156185336.6...@b28g2000cwb.googlegroups.com...

> Perplexed in Peoria wrote:
> > "Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message
news:1155980766....@m79g2000cwm.googlegroups.com...

> > > R Norman (I think) wrote:
> > > > You are
> > > > in the mode of multiplying small probabilities to get such a tiny
> > > > number that you can prove the final event to be impossible. That
> > > > argument has been shown repeatedly to be wrong because the events
> > > > involved are not independent so that the probabilities don't multiply.
> > >
> > > Interesting . . . Please do explain your notion of the statistics
> > > involved. Please do explain to me how events that are not independent
> > > (i.e., events that are *dependent* on each other) have a probability of
> > > occurrence that is not based on multiplying the probabilities of each
> > > individual event with each other?
> > >
> > > For example, what is the probability of flipping a quarter and landing
> > > it on heads 3 times in a row? Is it not 1/2 x 1/2 x 1/2 = 1/8?
> > >
> > > The events involved are not independent, that's true. They are
> > > dependent. ...
> >
> > Sean, you are just dead wrong. Which surprises me because IIRC
> > you did pretty well the last time a probability question came up.
> >
> > The events in three successive flips of a fair coin are _independent_.
> > That is why you can multiply the probabilities.
> >

> > [unsnipping two snipped paragraphs]

> > But now lets try flipping a bent quarter. The bending was done
> > 'randomly' - there is no more reason to suspect that the bending
> > favors heads than tails. If you wish, you can imagine that it
> > was flipped and then picked up without looking before inserting
> > it into the bending device.
> >
> > Now what is the probability of heads on the first flip. 1/2, I
> > think. But the probability of three heads is no longer 1/8.
> > The successive flips are not independent. They all depend on
> > the same datum - which way the coin is bent.
>
> The individual events are indeed independent events. However,
> realizing a specific *sequence* of variables is *dependent* upon the
> specific order in which the variables are realized. That's clearly
> been my whole position this entire time. I'm talking about the odds
> that a specific sequence will exist in a given genome. Those odds are
> calculated by multiplying the number of potential variables per
> position by the number of positions in the sequence in question - as in
> 1 in 20^100 for a specific 100-character residue sequence.

I hadn't intended to get dragged into the meat of this
controversy. My original intention was simply to point
out that you were wrong on the technicalities and technical
terminology of probability theory. That is a particularly
dumb thing to do when you do it in a paragraph laden with
sarcastic phrases like "Please do explain ...". You should
avoid doing that. It loses credibility.

But since you seem to want to persist in challenging R Norman
on the substance, let us look into the question as to whether
multiplying probabilities is the way to go here.

Ok, we have a number of proteins involved here, all of which
are complex, all of which do something, and all of which must
work in concert to do some bigger thing? Are we in agreement
so far?

Call the proteins A, B, C, etc. Call the 'probability of
the proteins' P(A), P(B), P(C), etc. We will get to what
these probabilities actually represent in a moment. What
you want to claim is that the probability of the whole
complex structure should be calculated as P(A) times P(B)
times P(C) etc. What I want to claim is that this algorithm
is wrong and that the real probability is much higher than
the one you are computing. Are we in agreement so far?

Ok, now what do we mean by these probabilities like P(A).
You want to claim that the right definition for P(A) is
the probability that some random sequence of amino acids
would result in a protein that that does the same thing
that protein A does. You will concede that there may
be many amino acid sequences that are functionally
equivalent to the 'true' A sequence. There is a certain
amount of slack allowed. You will concede this because
you know that evolutionists can point out many examples
of proteins where the sequence is slightly different from
one species to another, yet the two distinct proteins do
essentially the same thing. You are a reasonable man.
Yet you will insist that while there is some 'slack' in
a protein's sequence specification, there isn't enough
slack to make much of a dent in your argument. Are we
in agreement so far?

Ok, since you were so gracious in conceding that, I
will also be gracious. I will accept your definition of
P(A). I will concede that it is a small number. But
I haven't conceded yet that we should just go and
multiply P(A) times P(B) etc. First I want to look
more closely at P(A) in a rather unusual way.

Ignoring the 'slack' for the time being, you would say
that P(A) is itself a product - it is (1/20)^N where
N is the number of amino acids in the sequence and
the factor (1/20) is the chance that a 'random' amino
acid would be 'right'. Ok, I concede that, if one
ignores the fact that different amino acids have
different frequencies. It is not exactly right, but
close enough for bio-theology work.

But I want to break down P(A) into factors in a
different way. I want to define

P(A) = pAf * pAs * pAc
where
pAf is the probability that a random amino acid
sequence of the same length as A will fold
into a (mostly) stable shape. (Most random
sequences don't do that, you know.)
pAs is the probability that a random amino acid
sequence of the same length as A which folds
stably will also do something interesting.
(Most random folded sequences just sit there
you know.)
pAc is the probability that a random amino acid
sequence of the same length as A which both
folds stably and does something interesting
will do the correct thing - the same thing
that A does.

Do you understand and accept these definitions?

Ok, now to continue. You want to claim that
the right thing to do is to multiply out

P(A) * P(B) * etc.

which is the same thing as

(pAf * pAs * pAc) * (pBf * pBs * pBc) * etc.

Now, you have probably heard before that multiplying
is wrong because natural selection is involved and
that therefore pAc and pBc are not totally independent
probabilities. You may even be willing to concede
this because you think that independence still reigns
at the level of pAf vs pBf and of pAs vs pBs. Well,
I have to disagree. Because all of A, B, C, etc.
are descended from earlier proteins that were selected
by natural selection to fold and to do something
useful. And since gene duplication and divergence is
the way that evolution builds large proteins, by
the time evolution got around to building large
complex structures like flagella and cillia, there
were plenty of sequences around that already folded
stably and did something. All that was required was
to duplicate some of them (an easy, almost trivial
kind of mutation) and then to set to work changing
what they did into the new, correct thing to do.

Your claim of independence fails at all levels.
Are we in agreement so far?

Now, I suspect that you may be tempted to bring
up abiogenesis at this point. You might wish
to claim that my arguments here don't apply to
abiogenesis. And, you know what? You would be
right. But my arguments do apply to cilia and
flagella and clotting cascades and those kind of
things which no one thinks were invented yet at
the time of abiogenesis.

We can talk about abiogenesis some other day. You
can even talk some more about cilia and flagella.
I certainly haven't completely explained them here.
All I have done is to show that simple multiplication
of probabilities is not the way to approach these
kinds of evolved 'IC'.

r norman

unread,

Aug 21, 2006, 5:30:38 PM8/21/06

On 21 Aug 2006 13:57:16 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

That is NOT the question here, pit!

You wrote: "Please do explain to me how events that are not

independent (i.e., events that are *dependent* on each other) have a
probability of occurrence that is not based on multiplying the
probabilities of each individual event with each other?

I answered you with exactly such an explanation.

Seanpit

unread,

Aug 21, 2006, 5:58:11 PM8/21/06

It most certainly is the question. You are the one who told me that I
wasn't calculating the odds correctly. Well, my main point is that it
is hard to find specific sequences in sequence space at greater and
greater minimum size and specificity requirements. I've been
calculating the odds of this by taking the number of variables per
position and raising them to the power of the number of positions. You
seemed to be suggesting that this wasn't the propper way of doing
things. Well, Norm, please do explain?

> You wrote: "Please do explain to me how events that are not
> independent (i.e., events that are *dependent* on each other) have a
> probability of occurrence that is not based on multiplying the
> probabilities of each individual event with each other?
>
> I answered you with exactly such an explanation.

You didn't answer the main question - your initial assertion that I was
multiplying when I shouldn't be. Well, Norm, what are the real odds of
flipping a coin 10 times and having it realizing the specific sequence
HTTTHHHTTT? How do you go about figuring the odds for this problem? -
a problem where the "correctness" of each character in position is
*dependent* upon that character's relation to all the other characters
in the sequence. You see, the type of "dependence" I am talking about
is the dependency of each character to be in a specific location in a
sequence or in 3D space relative to all the other characters in that
sequence.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 6:06:22 PM8/21/06

I'm talking about the type of dependency where the function of the
system is dependent upon the specific arrangement of the characters in
a sequence. I'm not talking about the probability of a single position
ending up on a specific character. That event is an independent event
- which is what makes me able to multiply the odds together to
calculate the overall odds of realizing an entire sequence of specific
independent events.

> But this is
> true only for a series of independent events.

That's right - but Norm evidently doesn't seem to understand that
because he said I was wrong in my multiplying the odds of independent
events together to obtain the odds for a specific series of independent
events.

> That's what the argument
> is about. Norman was just trying to show the fallacy of your claim in a
> way that even you would understand easily. But you seem unwilling to
> apply that understanding to the general case. But here is the lesson
> again: probabilities can be multiplied only if they are independent. Did
> you get it that time?

That's true, but that isn't what I took Norm as arguing in his initial
counter. It seemed to me that Norm was arguing that my calculation of
the odds of realizing a specific series of independent events was wrong
because I multiplied the odds of each independent event. He seemed to
argue that I couldn't do what I was doing because the events I was
multiplying were not independent. The problem is, they are. They are
independent as individual events so I can multiply them.

The only thing I am arguing is "dependent" is the function's dependency
on the specific size and sequence order of the underlying residue(s).

Sean Pitman
www.DetectingDesign.com

r norman

unread,

Aug 21, 2006, 6:23:19 PM8/21/06

On 21 Aug 2006 15:06:22 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

What you do not know is that, because of the nature of chromosomal
mutations involving repeated segments and translocated regions and the
like, it is not at all true that adjacent (or even distant)
nucleotides are independent. The same goes for adjacent (or even
distant) amino acids in a protein. A sequence of nucleotides or a
sequence of amino acids is NOT a chain of independent events. Your
notion of a sequence space is totally flawed. Your calculations of
probability are totally flawed. It is very much true that, if events
are not independent, then it is usually incorrect to calculate a
probability by multiplying the probabilities of component events. The
elements of a sequence are by no means independent events. It is
flipping a series of coins that are all stuck together so that they
all have to fall one way or the other. If I glue together ten coins
all oriented in the same way and flip them, then the probability of
getting ten heads in a row is 1/2.

Seanpit

unread,

Aug 21, 2006, 7:05:18 PM8/21/06

Perplexed in Peoria wrote:

> > The individual events are indeed independent events. However,
> > realizing a specific *sequence* of variables is *dependent* upon the
> > specific order in which the variables are realized. That's clearly
> > been my whole position this entire time. I'm talking about the odds
> > that a specific sequence will exist in a given genome. Those odds are
> > calculated by multiplying the number of potential variables per
> > position by the number of positions in the sequence in question - as in
> > 1 in 20^100 for a specific 100-character residue sequence.
>
> I hadn't intended to get dragged into the meat of this
> controversy. My original intention was simply to point
> out that you were wrong on the technicalities and technical
> terminology of probability theory. That is a particularly
> dumb thing to do when you do it in a paragraph laden with
> sarcastic phrases like "Please do explain ...". You should
> avoid doing that. It loses credibility.
>
> But since you seem to want to persist in challenging R Norman
> on the substance, let us look into the question as to whether
> multiplying probabilities is the way to go here.
>
> Ok, we have a number of proteins involved here, all of which
> are complex, all of which do something, and all of which must
> work in concert to do some bigger thing? Are we in agreement
> so far?

Sure . . .

> Call the proteins A, B, C, etc. Call the 'probability of
> the proteins' P(A), P(B), P(C), etc. We will get to what
> these probabilities actually represent in a moment. What
> you want to claim is that the probability of the whole
> complex structure should be calculated as P(A) times P(B)
> times P(C) etc. What I want to claim is that this algorithm
> is wrong and that the real probability is much higher than
> the one you are computing. Are we in agreement so far?

I think you are going a little off base here. But, I'll go into that a
bit more later on.

> Ok, now what do we mean by these probabilities like P(A).
> You want to claim that the right definition for P(A) is
> the probability that some random sequence of amino acids
> would result in a protein that that does the same thing
> that protein A does.

That's true . . .

> You will concede that there may
> be many amino acid sequences that are functionally
> equivalent to the 'true' A sequence. There is a certain
> amount of slack allowed. You will concede this because
> you know that evolutionists can point out many examples
> of proteins where the sequence is slightly different from
> one species to another, yet the two distinct proteins do
> essentially the same thing. You are a reasonable man.
> Yet you will insist that while there is some 'slack' in
> a protein's sequence specification, there isn't enough
> slack to make much of a dent in your argument. Are we
> in agreement so far?

Yep . . .

> Ok, since you were so gracious in conceding that, I
> will also be gracious. I will accept your definition of
> P(A). I will concede that it is a small number. But
> I haven't conceded yet that we should just go and
> multiply P(A) times P(B) etc. First I want to look
> more closely at P(A) in a rather unusual way.

Ok . . .

> Ignoring the 'slack' for the time being, you would say
> that P(A) is itself a product - it is (1/20)^N where
> N is the number of amino acids in the sequence and
> the factor (1/20) is the chance that a 'random' amino
> acid would be 'right'.

Right . . .

> Ok, I concede that, if one
> ignores the fact that different amino acids have
> different frequencies. It is not exactly right, but
> close enough for bio-theology work.

Oh come on now . . . Do you really think this matters much as far as
the main point is concerned?

> But I want to break down P(A) into factors in a
> different way. I want to define
>
> P(A) = pAf * pAs * pAc
> where
> pAf is the probability that a random amino acid
> sequence of the same length as A will fold
> into a (mostly) stable shape. (Most random
> sequences don't do that, you know.)
> pAs is the probability that a random amino acid
> sequence of the same length as A which folds
> stably will also do something interesting.
> (Most random folded sequences just sit there
> you know.)
> pAc is the probability that a random amino acid
> sequence of the same length as A which both
> folds stably and does something interesting
> will do the correct thing - the same thing
> that A does.
>
> Do you understand and accept these definitions?

I think so . . .

> Ok, now to continue. You want to claim that
> the right thing to do is to multiply out
>
> P(A) * P(B) * etc.
>
> which is the same thing as
>
> (pAf * pAs * pAc) * (pBf * pBs * pBc) * etc.
>
> Now, you have probably heard before that multiplying
> is wrong because natural selection is involved and
> that therefore pAc and pBc are not totally independent
> probabilities. You may even be willing to concede
> this because you think that independence still reigns
> at the level of pAf vs pBf and of pAs vs pBs. Well,
> I have to disagree. Because all of A, B, C, etc.
> are descended from earlier proteins that were selected
> by natural selection to fold and to do something
> useful.

That's right . . .

> And since gene duplication and divergence is
> the way that evolution builds large proteins, by
> the time evolution got around to building large
> complex structures like flagella and cillia, there
> were plenty of sequences around that already folded
> stably and did something.

Correct . . .

> All that was required was
> to duplicate some of them (an easy, almost trivial
> kind of mutation) and then to set to work changing
> what they did into the new, correct thing to do.

That's right . . .

> Your claim of independence fails at all levels.
> Are we in agreement so far?

You seem to me, at this point, to be confusing ratio with starting
point. The ratio is still what it is. It seems to me that you are
simply suggesting that the starting points are much closer to the
targets than I seem to realize. Correct? Not nearly as many random
steps need to be taken as I seem to be suggesting - right?

Of course, I've argued that gene duplication does not make novel
starting points. It only makes more of the same starting point. You
are still left with having to cross a gap that includes all potential
sequences - even the ones that won't fold to make much of anything.
This might be taken to mean that the random walk/sampling required is
not significantly reduced.

Unless, unless of course the genome already has the needed part to make
the next step in the genome pre-formed. Your argument seems to suggest
that the odds that this will in fact be the case are pretty good! -
since many of the non-workable potential sequences are screened out
ahead of time by default. And, this is in fact true at lower levels of
functional complexity. However, at higher and higher levels, the size
of the step to the next novel function grows linearly. It becomes
harder and harder to find a pre-existing sequence that would cross this
step in one fell swoop with one single mutation event - such as a
duplication and insertion of just the right sequence into the correct
spot. The problem is that the odds that the needed sequence that would
fill the gap actually exists preformed in the same genome decrease
exponentially as well with each step up the ladder.

If you want to use a specific example, please do explain a specific
functionally beneficial step in the evolution of the flagellar system
from some proto form. Or, provide any actual experimental
demonstration of the evolution of any new function that require more
than a few thousand fairly specified bp of DNA.

It is true that all the parts needed to form a flagellar system of
motility exist in all bacteria. The question is, how does one get
these parts together in just the right way? The usable chucks just
aren't big enough. That's the problem. I mean, there might be 30aa that
would work in one place and another 42aa that would work in another
place and another 12aa that would work over there etc. How does one
get all of these small chunks together to form the next useful bigger
chunk system?

In considering this problem, one must also consider that multicharacter
mutations are much less common than point mutations or mutations
involving relatively short sequences. Getting a specific mutation of,
say, exactly 50 characters to be inserted into a specific spot is
extraordinarily rare regardless of if no specific 50 character sequence
is required - just 50 characters in any order.

Also, let's say a particular step requires a specific insertion into a
specific spot of a series of codons that would code for a fairly
specified 100aa sequence - with a ratio of about 1e-40? (see
calculations by Yockey and Sauer) What are the odds that this specific
sequence exists, preformed, somewhere in a genome of only 5-10 million
bp? Then multiply this times the odds of this specific sequence
getting copied out of its current location and pasted into the specific
needed location. How much time does this require - on average? What if
the gap is 100aa?

> Now, I suspect that you may be tempted to bring
> up abiogenesis at this point. You might wish
> to claim that my arguments here don't apply to
> abiogenesis. And, you know what? You would be
> right. But my arguments do apply to cilia and
> flagella and clotting cascades and those kind of
> things which no one thinks were invented yet at
> the time of abiogenesis.

Forget about abiogenesis. I'm only interested in evolutionary
potential given the starting point of a living creature that can
reproduce itself. I really don't think you've solved the problem. All
your theory does is create little islands that happen to link up with
each other like a sticky bubble gum. This does make evolution quite a
bit easier at very low levels - where pre-formed chucks of this can
combine with pre-formed chunks of that to make a novel functional
system. However, at higher and higher levels of minimum size and
specificity requirements, the odds that the right pre-formed chuck will
actually exist anywhere in the genome to get you to the next step in
the pathway toward any higher level system drop off exponentially - and
you are back to where you were to start with.

> We can talk about abiogenesis some other day. You
> can even talk some more about cilia and flagella.
> I certainly haven't completely explained them here.
> All I have done is to show that simple multiplication
> of probabilities is not the way to approach these
> kinds of evolved 'IC'.

I really don't think you've done what you think you've done at all.
The islands of potentially beneficial sequences simply become more and
more stretched out at higher and higher levels of functional complexity
until the bridges between them simply snap apart and they become truly
isolated in a very remote way. Now, no single multicharacter
insertion/deletion/translocation etc is going to get you there.
Multiple mutations involving multiple characters each are required.
And, multiplication of the odds is back . . . and at very low levels.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 21, 2006, 7:23:11 PM8/21/06

r norman wrote:

> What you do not know is that, because of the nature of chromosomal
> mutations involving repeated segments and translocated regions and the
> like, it is not at all true that adjacent (or even distant)
> nucleotides are independent.

They are as far as mutations go. Sure, natural selection weeds out a
lot of these mutations, but the mutations themselves are indeed pretty
much independent as far as relevance to the main point of this
discussion is concerned.

> The same goes for adjacent (or even
> distant) amino acids in a protein. A sequence of nucleotides or a
> sequence of amino acids is NOT a chain of independent events.

Mutations that have the potential to affect a residue sequence are
indeed independent events. That is what makes them "random". Now, the
result, if functional, will be acted on by nature. If the result is
negative, it will be removed by nature. This will have a biasing
effect on the types of mutations that can be long tolerated, but the
mutations themselves are pretty much independent random events.

> Your
> notion of a sequence space is totally flawed. Your calculations of
> probability are totally flawed. It is very much true that, if events
> are not independent, then it is usually incorrect to calculate a
> probability by multiplying the probabilities of component events.

Any reference for your notion that mutations that affect residue
sequences are not pretty much independent events?

> The
> elements of a sequence are by no means independent events. It is
> flipping a series of coins that are all stuck together so that they
> all have to fall one way or the other. If I glue together ten coins
> all oriented in the same way and flip them, then the probability of
> getting ten heads in a row is 1/2.

Do you really think mutations work like that? How about those mutations
that can hit and change one specific codon at a time? - as in point
mutations? Mutations do not usually change multiple codons at the same
time to the same code. Of course, there are frame-shift mutations,
that can and do change multiple codons at the same time. However, if
the original codon sequence didn't code for exactly the same repetitive
residue sequence (AAAAAAAAA), but rather a sequence like ATTTCGGCA, a
frame-shift mutation would not likely produce the same pattern - like
TAAGCCGT. More likely, it would produce a pattern completely
independent of the original sequence - completely random.

Sean Pitman
www.DetectingDesign.com

John Harshman

unread,

Aug 21, 2006, 8:33:51 PM8/21/06

Seanpit wrote:

If you can't get the simplest terminology straight, how can you expect
anyone to understand what you're trying to say?

Marc

unread,

Aug 21, 2006, 9:43:24 PM8/21/06

John Harshman wrote:
> Seanpit wrote:

......... snp

> > That's true, but that isn't what I took Norm as arguing in his initial
> > counter. It seemed to me that Norm was arguing that my calculation of
> > the odds of realizing a specific series of independent events was wrong
> > because I multiplied the odds of each independent event. He seemed to
> > argue that I couldn't do what I was doing because the events I was
> > multiplying were not independent. The problem is, they are. They are
> > independent as individual events so I can multiply them.
> >
> > The only thing I am arguing is "dependent" is the function's dependency
> > on the specific size and sequence order of the underlying residue(s).
>
> If you can't get the simplest terminology straight, how can you expect
> anyone to understand what you're trying to say?

I am beginning to wonder if Dr. Pitman is a mega-troll since he is
so very often twisting things out of their context in a calculated way.

Perhaps the whole thing - his web site, the threads on statistics, the
way he is arguing with me elsewhere in this thread that an individual
experiencing the "evolution" of an immune response is an example
of "biological evolution", is all a put-on to draw out replies and to
set
an example for how wrong some creation and ID arguments are.

In this sense, he is *trying* to get people to *not* understand his
arguments at all. (He is doing fairly well, too.)

The sad part is that I have a feeling he is ridgy-didge in his belief
and it is going to take more than revealing him as a troll to get
him to change his position.

(signed) marc

Von R. Smith

unread,

Aug 22, 2006, 1:46:45 PM8/22/06

Seanpit wrote:
> Von R. Smith wrote:
> > Seanpit wrote:
> > > Von R. Smith wrote:

<snip>

> > > >
> > > >

It sure looks like one.

> Exactly the same thing is going on
> with protein sequences. The sequence abcdef is equivalent to a protein
> made up of 6 specific residues arranged in a specific order.

Even if I took your word on this, a strong, accurate analogy is
nonetheless an analogy, and I specifically said that I wasn't
interested in analogies. If you are describing such a pervasive truism
in genetics and protein chemistry, why can't or won't you give me a
*real* example of a *real* genetic sequence that illustrates what you
are talking about?

> There
> would only be one such residue sequence in the sequence space of 20^6
> six-residue sequences.
>
> Coding for such a specific residue sequence with the use of an
> underlying DNA sequence would require just as much specificity in the
> underlying DNA. The underlying DNA code could code for any one of the
> 20^6 sequences. Getting it to produce a specific residue sequence out
> of all those possibilities requires an equivalent degree of
> specificity.
>
> If you think this is not true, what basis do you have for such a
> notion?

The problem is not that it is not true; the problem is that it does not
answer my question. You were supposed to be telling me what
*additional* constraints a "3D requirement" imposes on variability that
do not exist in the case of enzyme cascades; all you describe here are
the constraints on a nucleotide sequence if it is to code for a
particular peptide sequence. Since the structural genes for any
proteins, including enzymes, have exactly the same constraint (they
must follow the universal genetic code), my question to you remains
unanswered, even in analogy.

>
> > We have already dispensed with the notion that your "3D requirement"
> > for function imposes an actual requirement of sequence contiguity in
> > the genome.
>
> We have? The 3D requirement is still what must be coded for by the
> underlying DNA. Since there are many different possible 3D outcomes
> given the same protein sequence for certain proteins, the underlying
> DNA must be able to end up coding for the right 3D requirement with the
> use of chaperone proteins etc. In the end, it is still the specific
> final product that must be produced in order for the function in
> question to be realized.

I am still waiting for you to tell me, specificially, what *additional*
constraints this imposes on the underlying genetic sequence. All
genes, including those for enzymes, are constrained by the universal
genetic code if they are to produce a particular peptide sequence.
Most if not all genes have some sort of regulation controlling the
timing of their expression.

Chaperones, if needed, are just one more protein required for the
"function in question" to work. If you were simply trying to say that
a flagellum is more complex than a typical metabolic pathway because it
requires more proteins, we could have saved ourselves a lot of time.
But we both know that is not all you are trying to say; you want to
argue that a "3D requirement" imposes a *qualitative* difference in the
degree of constraint on genetic sequence. Invoking chaperones,
transport proteins, etc., does not do this; it merely adds to the total
number of proteins needed.

btw, there are only 3 or 4 chaperones, and about as many transport
proteins, associated with flagellar assembly, and they tend to be
small.

>
> > The genes coding for the flagellum in E. coli are spread
> > out over one million base-pairs of genome. The structural proteins of
> > the transport apparatus alone are coded for on operons more than 100
> > kbp apart. So there is no "abcdef" that distinguishes this function
> > with a "3D requirement" from functions that don't. In either case, the
> > genes coding for "abc" and "def" could be a large distance from one
> > another. In eukaryotes, there isn't even an "abcdef" analog within
> > individual genes.
>
> Sure there is because the intron segments are spliced out in very
> specific ways in order to make the abdef analog. Again, the final
> product is the important target here. The DNA specificity cannot be
> less than the specificity required by the final product. You can't
> have the DNA option of coding for just any 6-character residue
> sequence. You must have the DNA be able to code for one specific
> 6-character sequence. How is this done if the DNA itself isn't just as
> specified as the final product? Any other specific 6-character
> sequence could be coded for. The fact that one is coded for requires an
> equivalent degree of specificity.

Again, all you describe here is the need to follow the universal
genetic code. You're still short of any actual description of an
actual constraint on genetic sequence that is *unique* to functions
with a particular "3D requirement". I've given you a short list of
parameters that one could vary to produce distinct genetic sequences.
I'll give them to you again, in even more condensed form:

-the variability within the coding sequences (and regulatory sequences)
of individual genes contributing to a given function
-the relative order of a group of genes contributing to a given
function
-the amount and internal variability of "genetic real-estate" between
those genes

Feel free to name any other parameters I might have forgotten.

This is not hard, Sean. I've broken it down to a manageable number of
possibilities. Now tell me: which of these parameters is
exponentially more constrained if a function has a "3D requirement",
and in what way is it more constrained?

>
> > So let's try this again: What actual constraints on genetic sequence
> > exist for a function with a "3D requirement" that don't exist for
> > genetic sequences coding for other types of functions, such as enzyme
> > cascades? How are these genetic sequences more specific? Once more:
> > I don't want another analogy. I want an actual description of an
> > actual difference in genetic sequence.
>
> Why don't you tell me how it would be possible to code for a specific
> 6-residue sequence without the underlying DNA sequence being just as
> specified. You can use an analogy if that helps you.
>
> Yes or no, couldn't the underlying DNA sequence code for any one of
> 20^6 sequences in 6-residue sequence space? How would the DNA be able
> to hit upon just one of them in particular? Please do explain your
> position?

I'll answer your questions after you have answered mine. All you are
talking about here is the need for a gene encoding a peptide to follow
the universal genetic code. This constraint exists for *every* gene,
so it does not answer my question, which is about what *special*
constraints you think are peculiar to a sequence coding for a function
with a "3D requirement".

Seanpit

unread,

Aug 23, 2006, 11:22:00 AM8/23/06

John Harshman wrote:

> > The only thing I am arguing is "dependent" is the function's dependency
> > on the specific size and sequence order of the underlying residue(s).
>
> If you can't get the simplest terminology straight, how can you expect
> anyone to understand what you're trying to say?

My terminology was correct in the context of the discussion. Norm used
the correct terminology, but attached it to the wrong concepts. I was
trying to show him that the sequence variables really are independent
while, at the same time, the function of the system is dependent upon a
specific order of the statistically independent variables.

Sean Pitman
www.DetectingDesign.com

r norman

unread,

Aug 23, 2006, 11:40:12 AM8/23/06

On 23 Aug 2006 08:22:00 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

"Norm" is Richard Norman, if you please. And the concepts that are
wrong are all yours. Your example of flipping coins is, in the
tradition of coin flipping, an example of independent trials even
though you said otherwise and a skilled flipper can introduce
significant correlations between consecutive flips. It is your claim
that consecutive elements in a nucleotide sequence or an amino acid
sequence are independent that is wrong. That is true whether or not
there is a specific order to the sequence.

Seanpit

unread,

Aug 23, 2006, 12:08:30 PM8/23/06

z wrote:

< snip >

Note that the genes for the flagella are not turned on until after the
hook is complete. That's my point. The flagellum would not
self-assemble properly if all the parts were put in the same location
at the same time.

Beyond this, the specific 3D structure is dependent upon an equivalent
degree of code complexity in the DNA sequencing. An almost infinite
number of different potential structures of equivalent size could be
coded for by DNA. The requirement for a very specific 3D structure
that produces the motility function occupies a very very small part of
the potential of what could be produced that simply wouldn't work as a
flagellar motility system.

> >relative to the other enzymes in the cascade, is not required for the

> >function of the cascade to work. This is not true of the systems like
> >the flagellar motility system where all the individual parts do require
> >orientation relative to all the other parts.
>
> You miss the point. There is a huge amount of structural information
> required to "specify" an enzymatic cascade. The active site of each
> enzyme must recognize both the substrate and the product of the
> reaction.

That's true. Each individual enzyme in a cascade may indeed require a
great deal of specific order to its individual residues relative to
themselves within that enzyme. However, the overall function of the
enzymatic cascade does not require the additional requirement that each
individual enzyme be specifically arranged in 3D space relative to all
the other enzymes. A flagellar motility system does have this
additional specificity requirement - which makes an exponential
difference in the rarity of such a system in the potential of sequence
space.

> >We are talking about systems of function here. Sure, relatively simple
> >systems of function that only require a single small protein sequence
> >aren't much of a problem. However, when it comes to more complex
> >systems of function, functions that require multiple proteins all
> >working together in a specific arrangement with each other at the same
> >time, then you start running into a few problems when it comes to
> >evolvability. The size and specificity of such multiprotein systems
> >makes them extremely rare and therefore unlikely to find in the
> >potential of sequence space.
>
> Sequence space doesnt look at protein-protein interaction. It merely
> is a description of the sequence of a protein and its neighbors.

That's true.

> We have looked at a large number of crystal stuctures of a particular
> class of proteins that have natuarlly evolved to bind to a particular
> surface on a particular protein with exquisite specificity. Us
> biology types like to call thses evolved proteins antibodies.

You need to talk to Marc about antibody evolution. Marc says that
antibody evolution doesn't count as real evolution. But, that is Marc
for you. Personally, I agree with you that improvement in antibody
specificity over time, via random mutation and function-based
selection, is indeed real evolution in action. However, there is just
one little problem with this sort of evolution.

The problem with antibody evolution is that it is template-based. All
that has to happen is for a very small change in the antibody sequence
to result in a better match to a pre-established non-self antigen
sequence for a selective advantage to be realized. The odds of an
improved binding match to a pre-established template being realized are
actually quite good.

For example, it is pretty much the same thing as Dawkins did with his
"Methinks it is like a weasel" evolution algorithm. The offspring of a
completely random sequence that produced a single position with a
closer match to "Methinks . . ." were preferentially chosen out and
given increased reproductive advantages over their peers. And, because
of this, over just a few generations the exact phrase "Methinks it is
like a weasel" quickly evolved.

Exactly the same thing happens with antibody evolution. Each
generation of immune cells produces a range of variations of
antibodies. Those cells that produce just a little better match are
preferentially chosen out from among their peers to receive a
reproductive advantage. Very quickly, antigen specificity is improved
over time.

While I would accept this as real evolution in action, unlike Marc, it
is template-based evolution. Not all types of functions can be built
up in this manner. For example, how would a flagellar motility system
be build using a template? There simply is no template upon which
every single residue position change can be selected as an improvement
or a deterioration of the flagellar motility function. Flagellar
motility simply can't be realized in any incremental degree until a
very large number of residues are correctly arranged to begin with.
Obtaining this minimum requirement can only be done via an extensive
random walk through a host of non-beneficial options - from any
starting point a non-flagellate genome may have.

> Your body can in a span of a few weeks produce an antibody to almost
> any foreign protein. Real time protein evolution in that the
> resulting antibody will contain sequences that are different from
> anything in your germ line.

That's true, but it's all based on template matching . . .

> Protein-protein interactions are easy to evolve. While ther are
> examples of proteins that actually swap bits of secondary structure to
> form quaternary structure, for the most part it's just two surfaces
> sticking together. You fixate on this as if it's a big deal-
> something that caused me to scratch my head and wonder why. Getting a
> protein to recognize a small moleule and actually do something with it
> is far trickier.

For a single protein - yes. However, when you starting talking about
dozens of specific proteins needing to stick to each other in very
specific ways, the statistics involved start really adding up. We
aren't just talking about simply getting one protein to stick to
another in just any old way. We are talking about dozens of proteins
sticking to each other in a very specific way that cannot be built up,
one tiny residue change at a time, via template-type matching.

> >> We have fairly large datasets now. It's very clear that there are a
> >> smallish numeber (say ~100) of protein folds that are found commonly
> >> in biological systems. And its quite clear that they can be very
> >> divergent in sequence and still have the same 3D structure.
> >
> >That's also true. However, when it comes to higher and higher levels
> >of minimum system requirements the non-beneficial ways in which these
> >"smallish" number of folds can be arranged relative to each other
> >increases exponentially faster than the very small number of ways that
> >will actually work to perform a given function - like flagellar
> >motility.
>
> Expectations are everything. If you expect that you can get a fully
> functionally flagellar motility system all in one go, sure you'd be
> disappointed. The cooption of other prexisiting simpler systems has
> been presented and ignored by you so I won't elaborate further.

Where have you or anyone else shown that the simpler subsystems you
proposed can be easily stuck together in just the right way to reach
the next beneficial steppingstone function in your proposed pathway
with just a handful of residue changes? You make these bald claims
that such a detailed description has been delivered, but this is just
hot air. Where is this description? I have yet to read anything of
the sort.

Perhaps the one who comes the closest to such a description is Matzke's
attempt. He does better than I've seen anyone else do; yet even his
attempt is sorely inadequate. I go into some detail discussing
Matzke's paper at:

http://www.detectingdesign.com/flagellum.html

> >I'm asking for a what it takes to achieve a particular function.
> >Functions that do not require their parts to be in a specific
> >arrangement with each other are much much easier to evolve,
> >exponentially so, than those function that do require specific
> >arrangement of each of their parts with all the other parts in the
> >system.
>
> Again, expectations. Evolutionary theory does not predict that a
> flagellar motiltiy system just up and put itself together all at once
> due to one organism experiencing one selective event.

I'm not asking for someone to demonstrate the flagellar motility system
evolving all at once. I'm just asking for a demonstrating of just one
of your proposed steps in flagellar evolution. If you think a couple
subparts could easily evolve the ability to stick together, as in the
antibody system, to achieve the next step in the proposed pathway, then
please, show me the money! It is my position that such a step could
not be realized like you imagine because it could not use any sort of
pre-established step-by-step template to realize the proper link-up
mutations.

> Think modular, and think cooption.

Oh, I am I am . . . it just doesn't help. Too many changes to
pre-existing modules would need to be realized before any single step
in the evolution of a flagellar system could be realized.

< snip >

> Oh, and did your designer leave any other "traces" besides the
> bacterial flagella? It seems to the only specified example you toss
> out.

Translation, transcription, pinocytosis, basic vision systems, vascular
systems, ATP synthesis, etc. Every living thing requires very
high-level systems of function in order to exist - none of which can be
produced by random mutation and function-based selection. They simply
aren't template based.

Seanpit

unread,

Aug 23, 2006, 12:14:44 PM8/23/06

r norman wrote:
> On 23 Aug 2006 08:22:00 -0700, "Seanpit"
> <seanpi...@naturalselection.0catch.com> wrote:
>
> >
> >John Harshman wrote:
> >
> >> > The only thing I am arguing is "dependent" is the function's dependency
> >> > on the specific size and sequence order of the underlying residue(s).
> >>
> >> If you can't get the simplest terminology straight, how can you expect
> >> anyone to understand what you're trying to say?
> >
> >My terminology was correct in the context of the discussion. Norm used
> >the correct terminology, but attached it to the wrong concepts. I was
> >trying to show him that the sequence variables really are independent
> >while, at the same time, the function of the system is dependent upon a
> >specific order of the statistically independent variables.
>
> "Norm" is Richard Norman, if you please. And the concepts that are
> wrong are all yours. Your example of flipping coins is, in the
> tradition of coin flipping, an example of independent trials even
> though you said otherwise and a skilled flipper can introduce
> significant correlations between consecutive flips.

If such a thing happened, then the outcomes wouldn't really be "random"
now would they? The fact is that mutations that affect DNA are indeed
pretty much random events. They are not directed by any sort of
"skilled flipper". Your notions that genetic mutations are not
independent events is simply misguided.

> It is your claim
> that consecutive elements in a nucleotide sequence or an amino acid
> sequence are independent that is wrong. That is true whether or not
> there is a specific order to the sequence.

You are quite mistaken Richard. Each position in a sequence of
nucleotides and amino acids is indeed independent as a truly random
mutation could change any position to another character in a truly
random way. That is the basis of evolutionary theory. Mutations have
to be non-directed and truly random. Natural selection is supposed to
be the non-random force here - not mutations.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 23, 2006, 12:22:36 PM8/23/06

Von R. Smith wrote:

< snip >

> > Exactly the same thing is going on

> > with protein sequences. The sequence abcdef is equivalent to a protein
> > made up of 6 specific residues arranged in a specific order.
>
>
> Even if I took your word on this, a strong, accurate analogy is
> nonetheless an analogy, and I specifically said that I wasn't
> interested in analogies. If you are describing such a pervasive truism
> in genetics and protein chemistry, why can't or won't you give me a
> *real* example of a *real* genetic sequence that illustrates what you
> are talking about?

Pick any real genetic sequence you want. It will work exactly the same
way. It is simply a difference in the number of potential characters
per position. English has 26 options per position while residues have
20 and DNA has 4. Just plug in the different numbers to the same
formula. There is no fundamental difference Von.

The fact remains that if a system requires a specific 3D order of all
the residues in a sequence, this requirement makes such a system
extremely rare in the potential of the space that includes all
potential 3D arrangements of a certain number of residues. In order
for the underlying code to actually end up producing one specific
arrangment out of an almost infinite number of other non-beneficial
options the underlying code must also be equivalently specified.

I'm not sure that I can make it any more clear than that.

Seanpit

unread,

Aug 23, 2006, 12:39:43 PM8/23/06

Von R. Smith wrote:

> Sean will disown his strawman thrice before the cock crows if he's
> called on it, but as soon as he finds it opportune, he will
> re-introduce it right back into the discussion. For example, when
> trying to downplay the implications a real-time example of evolution
> such as the 2,4-DNT cascade for his claims, he will hasten to point out
> that such evolution is no big deal, since the individual enzymes could
> be independently useful, and be tacked on to the cascade one step at a
> time; apparently, actual examples of "our" version of evolution do not
> count as actual examples of "our" version of evolution for Sean.

They do count as examples of real evolution in action. They just don't
count as higher levels of evolution in action - as I've explained to
you exhaustively. Cascading systems do not require nearly the same
level of specificity as does a system that requires all of its parts to
be specifically arranged with each other in 3D space.

> On the other hand, when trying to play up the complexity of the
> flagellum, he will point out that one needs all of the 20-odd
> structural proteins, plus the supporting cast of chaperones, transport
> proteins, etc., for it to work.

That's not all. Not only does a flagellar system need all of its
parts, it needs all of its parts to be specifically arranged with each
other in three dimensions.

> Sean won't address (or even
> acknowledge unless pointed out) the fact that sub-components of the
> flagellum have recognizable independent uses, or that most of the
> individual proteins have identifiable non-flagellar homologs, or that
> one can propose plausible independent functions for the ancestors of
> those proteins.

This is a deliberate lie. I have addressed this point extensively both
in this forum and on my website. Of course the flagellar system is
made up of subsystems that do or may have plausible independent
usefulness. I've never said otherwise and you know it. Why present
this strawman to misrepresent my position in such a deliberate way?

> He'll simply insist that somewhere, somehow, there must
> be a neutral gap of several thousand base pairs of genetic code that
> must be crossed.

Show me otherwise. Show me where any of your subsystem parts are close
enough to overcome the non-beneficial/neutral gap problem? You simply
assert, without any evidence whatsoever, that the subparts are close
enough to each other to simply connect in just the right way with only
a handful of minor changes. Where is your evidence, theoretical or
factual, to back up this otherwise bald assertion?

> He will then go right back to arguments that model
> his strawman version of evolution, while continuing to deny that this
> is the only model he ever presents any actual arguments against.

I've never built a strawman to represent your version of how evolution
works. Your version supposes that the non-beneficial gaps simply do
not exist to any significant degree - leaving random mutation and
natural selection well able to cross over given a few million years.
That is your version of how evolution works - your real version. There
is no strawman misrepresentation of your views here. I am just
proposing that your views, your real views, are wrong. That the
non-beneficial gaps do indeed exist to such an extent that your version
would simply be untenable this side of a practical eternity of time.

You may say that my views are wrong here, but you really can't say that
I'm building a strawman to misrepresent your true position - unless you
don't understand the definition of a strawman argument (aka Howard
Hershey)

> The
> only excuse I have seen him give for steadfastly
> ignoring "our" version of evolution in any of his calculations of how
> long is the failure of scientists to demonstrate any real-time examples
> of any of the hypothetical intermediate evolutionary steps. (There are
> such examples, but he has excuses to cover those, too.)

Where are these examples Von? Where has anyone set up one of your
non-flagellate protosystems and shown them to merge together to form
any subsequent step in your proposed pathway?

You're just making this stuff up as you go along - hoping that mere
bluster will be good enough to prop up your baseless position . . .

< snip >

Sean Pitman
www.DetectingDesign.com

r norman

unread,

Aug 23, 2006, 1:30:10 PM8/23/06

On 23 Aug 2006 09:14:44 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

You are exposing ever more ignorance of probability theory. Just
because successive events are correlated does not mean that a process
is not "random". Just because the possibilities in a random process
are not uniformly distributed, every outcome being equally likely,
does not mean that the process is not random.

There are substitution mutations that do seem to be quite independent
events, although not every substitution is equally likely nor is the
probability of mutation the same at all sites. Still, one mutation is
independent of another. There are other mutations where snippets of
DNA are repeated or deleted or moved to another location or inverted.
In this case, what happens at one site is not at all independent of
what happens at the adjacent site. That is why we talk of protein
"motifs" and "gene families" The occurrence of a specific mutation
affecting a particular character or trait does not seem to be
associated with any aspect of that trait so that mutations are not
"directed" in a particular direction with regard to the final outcome.
That does not mean that every single nucleotide is completely
independent of every other nucleotide in every possible mutation.

There are also interesting complications involving mutational "hot
spots" which seem to be much more easily modified plus environmental
situations that cause cell biochemical changes that influence the
effectiveness of DNA error detection and repair mechanisms. No, the
actual occurrence of mutations is not at all the same as successive
flips of an unbiased coin determining nucleotide sequences. But you
are not likely to accept any of this, either.

Von R. Smith

unread,

Aug 23, 2006, 2:30:15 PM8/23/06

Seanpit wrote:
> Von R. Smith wrote:
>
> < snip >
>
> > > Exactly the same thing is going on
> > > with protein sequences. The sequence abcdef is equivalent to a protein
> > > made up of 6 specific residues arranged in a specific order.
> >
> >
> > Even if I took your word on this, a strong, accurate analogy is
> > nonetheless an analogy, and I specifically said that I wasn't
> > interested in analogies. If you are describing such a pervasive truism
> > in genetics and protein chemistry, why can't or won't you give me a
> > *real* example of a *real* genetic sequence that illustrates what you
> > are talking about?
>
> Pick any real genetic sequence you want.

I'm asking *you* Sean. It's your claim. So the onus is on you to
present actual examples of what you are talking about, and to
demonstrate that they actually support your point. If you can't, just
say so. If you can, now is the time to do so. Put up or shut up.

> It will work exactly the same
> way. It is simply a difference in the number of potential characters
> per position. English has 26 options per position while residues have
> 20 and DNA has 4. Just plug in the different numbers to the same
> formula. There is no fundamental difference Von.
>
> The fact remains that if a system requires a specific 3D order of all
> the residues in a sequence, this requirement makes such a system
> extremely rare in the potential of the space that includes all
> potential 3D arrangements of a certain number of residues. In order
> for the underlying code to actually end up producing one specific
> arrangment out of an almost infinite number of other non-beneficial
> options the underlying code must also be equivalently specified.
>
> I'm not sure that I can make it any more clear than that.

You can make it more clear by answering my questions, rather than
hand-waving around them: *How* does the "specific 3D order" make the
sequences that can code for it more rare? What aspects of it are more
rare, more constrained, more "specific"? What peculiar constraints on
genetic sequence does such a requirement impose, Sean? Where are they?
I've already listed a finite number of parameters that you can choose
from for producing distinct genetic sequences. You keep snipping them
without comment, so I will post them again:

-the variability within the individual genes coding for the relevant
proteins
-the relative location of these genes to one another on the genome
-the variability and placement of some other genetic sequence some
place else.

You can "make it more clear" by telling me which of these parameters
you think are more constrained, why you think they are more
constrained, and in what way they are more constrained.

Von R. Smith

unread,

Aug 23, 2006, 4:03:03 PM8/23/06

Seanpit wrote:
> Von R. Smith wrote:
>
> > Sean will disown his strawman thrice before the cock crows if he's
> > called on it, but as soon as he finds it opportune, he will
> > re-introduce it right back into the discussion. For example, when
> > trying to downplay the implications a real-time example of evolution
> > such as the 2,4-DNT cascade for his claims, he will hasten to point out
> > that such evolution is no big deal, since the individual enzymes could
> > be independently useful, and be tacked on to the cascade one step at a
> > time; apparently, actual examples of "our" version of evolution do not
> > count as actual examples of "our" version of evolution for Sean.
>
> They do count as examples of real evolution in action. They just don't
> count as higher levels of evolution in action - as I've explained to
> you exhaustively. Cascading systems do not require nearly the same
> level of specificity as does a system that requires all of its parts to
> be specifically arranged with each other in 3D space.

You and I must have a different understanding of what it means to
"explain" something. Apparently, you think it is a synonym for
"assert". I have repeatedly asked you to explain *how* your "3D
requirement" constrains sequence variability in ways that enzyme
functions do not. To date, you have not only not "explained this
exhaustively", you have largely evaded the question.

>
> > On the other hand, when trying to play up the complexity of the
> > flagellum, he will point out that one needs all of the 20-odd
> > structural proteins, plus the supporting cast of chaperones, transport
> > proteins, etc., for it to work.
>
> That's not all. Not only does a flagellar system need all of its
> parts, it needs all of its parts to be specifically arranged with each
> other in three dimensions.

...and I am still waiting for you to describe the constraints on
*sequence* variability that this imposes.

>
> > Sean won't address (or even
> > acknowledge unless pointed out) the fact that sub-components of the
> > flagellum have recognizable independent uses, or that most of the
> > individual proteins have identifiable non-flagellar homologs, or that
> > one can propose plausible independent functions for the ancestors of
> > those proteins.
>
> This is a deliberate lie. I have addressed this point extensively both
> in this forum and on my website.

As with the word "explain", you and I apparently have rather different
notions of what it means to "address" an issue.

> Of course the flagellar system is
> made up of subsystems that do or may have plausible independent
> usefulness. I've never said otherwise and you know it. Why present
> this strawman to misrepresent my position in such a deliberate way?

Your behavior here bears out my characterization of it to a tee: "Sean

will disown his strawman thrice before the cock crows if he's called on

it".

As for your slippling it right back into the discussion as soon as you
find it opportune, here is an example from this very thread since I
posted the above:

quote
[z wrote:]

[and you responded:]

For a single protein - yes. However, when you starting talking about
dozens of specific proteins needing to stick to each other in very
specific ways, the statistics involved start really adding up.

end quote

The only way that "the statistics involved start really adding up" is
if evolution of the function in question must evolve via your strawman.
If the steps were individually selectable, then the involvement of a
dozen or more proteins would not be a real problem for evolution. But
here as in so many other posts you fail to note that distinction;
rather, you argue from the unstated assumption that a function
involving interactions among many different proteins must hit upon all
those interactions at once. Likewise, this strawman seems to be the
unacknowledged basis for your whole "four 6s in a row" vs. "two pairs
of two 6s" analogy; again, you are trying to suggest that the proteins
in a function with a "3D requirement" must come into existence all at
once, rather than appear gradually. If you disagree, then tell me what
else your "four 6s in a row" actually refers to.

>
> > He'll simply insist that somewhere, somehow, there must
> > be a neutral gap of several thousand base pairs of genetic code that
> > must be crossed.
>
> Show me otherwise. Show me where any of your subsystem parts are close
> enough to overcome the non-beneficial/neutral gap problem? You simply
> assert, without any evidence whatsoever, that the subparts are close
> enough to each other to simply connect in just the right way with only
> a handful of minor changes. Where is your evidence, theoretical or
> factual, to back up this otherwise bald assertion?

Neutral gaps are your hypothetical construct, Sean. The burden to
demonstrate that they exist is on you. If you want to say you don't
buy evolution, fine. If you want to say that the failure to rub your
face in a real-time example of a flagellum evolving from scratch is
enough to satisfy you that your skepticism is well-founded, fine.

But we both know that your position goes beyond mere skepticism; it
relies on the *positive* claim that evolution beyond a certain level
*can't* happen in the available time, and positive claims require
positive evidence to support them. I have given you an example or two
of what lines of positive evidence might help your claim, one being to
demonstrate that the protein and genetic sequences we find in biology
tend to be randomly distributed throughout their respective sequence
spaces. That they are not thus distributed, but rather tend
overwhelmingly to nest in a hierarchical fashion expected by ToE is a
significant piece of evidence "to back up this otherwise bald
assertion."

>
> > He will then go right back to arguments that model
> > his strawman version of evolution, while continuing to deny that this
> > is the only model he ever presents any actual arguments against.
>
> I've never built a strawman to represent your version of how evolution
> works. Your version supposes that the non-beneficial gaps simply do
> not exist to any significant degree - leaving random mutation and
> natural selection well able to cross over given a few million years.
> That is your version of how evolution works - your real version. There
> is no strawman misrepresentation of your views here. I am just
> proposing that your views, your real views, are wrong. That the
> non-beneficial gaps do indeed exist to such an extent that your version
> would simply be untenable this side of a practical eternity of time.

Ah, but you always seem to miss the crucial part of the argument:
demonstrating that there is any basis for supposing such gaps to exist.
You simply assert that they do, and then proceed with the pretense
that that is the only model you need to argue against to show that
evolution can't happen this side of zillions of years.

>
> You may say that my views are wrong here, but you really can't say that
> I'm building a strawman to misrepresent your true position - unless you
> don't understand the definition of a strawman argument (aka Howard
> Hershey)

I do not think you are in any position to fault other people's grasp or
use of terms. The accusation of a strawman rests upon your repeated
use of it as your model for what the evolution of complex structures
and functions entails. Once it is pointed out that you are *not*
entitled to assume that evolution of complex functions must proceed by
your strawman version of it, all that is left of your argument is bare
incredulity and rejection.

>
> > The
> > only excuse I have seen him give for steadfastly
> > ignoring "our" version of evolution in any of his calculations of how
> > long is the failure of scientists to demonstrate any real-time examples
> > of any of the hypothetical intermediate evolutionary steps. (There are
> > such examples, but he has excuses to cover those, too.)
>
> Where are these examples Von? Where has anyone set up one of your
> non-flagellate protosystems and shown them to merge together to form
> any subsequent step in your proposed pathway?

I have already given you examples, in fact Matzke alludes to two of
them himself in his article: the evolution of elective suppression of
pilus-terminal adhesins to facilitate random dispersal, and changes in
the shape and size of the hook and filament to make it more optimal for
motility. Howard Hershey also gives examples of re-evolving the
protein-protein interactions between fliF and fliG. I pointed these
out to you on at least two other occasions, and you have never
commented, at least not in response to me.

>
> You're just making this stuff up as you go along - hoping that mere
> bluster will be good enough to prop up your baseless position . . .

Project much?

Marc

unread,

Aug 24, 2006, 11:17:31 AM8/24/06

Seanpit wrote:
> z wrote:

........................... snp.....

> > We have looked at a large number of crystal stuctures of a particular
> > class of proteins that have natuarlly evolved to bind to a particular
> > surface on a particular protein with exquisite specificity. Us
> > biology types like to call thses evolved proteins antibodies.
>
> You need to talk to Marc about antibody evolution. Marc says that
> antibody evolution doesn't count as real evolution. But, that is Marc
> for you. Personally, I agree with you that improvement in antibody
> specificity over time, via random mutation and function-based
> selection, is indeed real evolution in action. However, there is just
> one little problem with this sort of evolution.

It's *not* evolution. Are you *really* this thick? That's why I am
starting to think you are an exceptional troll. This is a put-on,
right?

Where does an antibody come from in the genome?

How is it encoded?

How many antibody genes are there?

What chromosomes are they on?

How do they produce receptors?

In what ways do the genes for antibodies and for the antigen receptors
on T-lymphocytes differ? In what ways are they the same?

How goes genomic evolution produce new antibody binding
pockets over time? Do you know what "hypermutation" is?

What is evolution? Where does evolution occur and how?

In what way does shifting the patterns of the antibodies produced
in an individual of almost any vertebrate species impact on the
heredity of that individual with respect to the ability of future
generations to produce new or different antibodies?

> The problem with antibody evolution is that it is template-based. All
> that has to happen is for a very small change in the antibody sequence
> to result in a better match to a pre-established non-self antigen
> sequence for a selective advantage to be realized. The odds of an
> improved binding match to a pre-established template being realized are
> actually quite good.

B-cells (the antibody producing lymphocytes named for a chicken's
"bursa of Fabricius") use the antibody as a cell surface receptor and
hypermutation of the binding site does improve binding for some
of the daughter cells, which then are more likely to have continued
engagement of the receptor allowing for more cell division. Or the
antigenic stimulus goes away and then this process dies down as
the immune response abates. If an antibody is produced in large
enough amounts, then it itself becomes a target of an anti-idiotype
immune response which sort of balances things out. (No evolution.)

Your "quite good" odds are not completely right here, Dr. Pitman.
All of the variations where binding is less strong just get less of
an antigenic signal to have them continue clonal expansion, so
they don't. Your "wisdom" here shows off your ignorance. And what
about the T-cell receptors, Dr. Pitman. Why don't they follow the
somatic hypermutation "evolution" system? Since they don't, and
since the next generation of offspring will need to build up the
"not-anti-self" potential T-cell repertoire all over again by thymic
education (positive and negative selection alongside tolerance)
in what way does the B-cell shift in pattern contribute to the species
evolution while the T-cell can't? The seven genes involved all work
the exact same way - segments for the "constant" and "variable"
regions brought together by recombination, with "joining", "diversity"
and random nucleotide insertion creating the CDR3 regions which
are in fact the antigen binding pockets. The alpha, beta, gamma and
delta T-cell receptor chains and the gamma, kappa and lambda chains
for the antibody, encoded in various location (one even inside another)
all function in the same way as a rachet-set functions in your tool
box.

Other tools compare with genes in a one-to-one way, or perhaps
in a few-to-one way. The "hammer" gene produces a hammer.
The "saw" gene likewise a saw. There are some forms of genes
for "screwdrivers" where the phillips-head is one form and the
standard screwdriver is the other (splice variants). Antibodies
and TcRs are like the combination of handle, extender and
imperial or metric socket that the rachet set has... a few simple
pieces that produce thousands upon thousands of different
specific tools. The trouble is, that your tool box has *no way*
to know which combination of handle, extender and socket was
used when I last opened my tool box. (It isn't evolution, Doctor.)

The difference here is in the extender bit. The metric and imperial
socket differences work well in this analogy because the "V"-gene
segments do work in a fashion like that - there are a few dozen of
these segments and many have just a couple of allelic variants so
the population contains a number of differing "haplotypes" where a
few metric sockets are available, then a few imperial and so on, in
a fashion where the immune repertoire you can produce in real life
differs from me (all other things - MHC and self components - being
equal). Things in evolution like bacterial and viral superantigens have
shaped the system this way so each of us has such a unique immune
repertoire that no one pathogen (yet) can take us all down at once.
(And I'll cite *myself* here on TcR haplotypes to back this up: "T cell
receptor beta chain genotyping in Australian relapsing-remitting
multiple sclerosis patients." Mult Scler. 2000 Jun;6(3):140-7.
PMID: 10871824 .... by M.M. Buhler et al.)

Now, the "extender" in your tool box (or mine) fails in this analogy
(or it needs to be explained a bit better). Between the constant and
variable segments is where the Complementarity Determining Region
# 3 is formed - the "CDR3", which is the antigen binding pocket.

Much smaller segments of genetic code form the Joining and the
Diversity segments, and random nucleotide insertion also occurs,
so as each lumphocyte progresses along a path towards maturity
it forms a unique bit of it's genome on just one chromosome where
the DNA between the "C" and "D" and between the "D" and "J" and
between the "J" and "V" segments are actually spliced out as small
rings of unwanted DNA. (How can it help species evolve when all the
stuff in between is lost?) Now, this is happening on just one of the
two chromosomes. The other is told not to do a thing (more or less,
search PubMed for "allelic exclusion" to learn more about this). With
a unique set of nucleotides making a CDR3 on one chromosome and
with the other chromosome doing nothing at all, each and every
lymphocyte is a completely unique creation of micro-genetic change
that is not reflected in the germline or in the gene pool. (It isn't a
part
of what biologists refer to as "evolution of a species", Dr. Pitman.)

If you were cloned from a lymphocyte, one of your chromosomes
would be missing a number of "V" genes, perhaps the "C" gene that
was in between if you used the farther one, and some other bits.

Where do those lost bits go in your model of evolution, Dr. Pitman?

Of course, you would inherit a CDR3 binding pocket in your genome
and with that (plus allelic exclusion, which would still apply) you now
would only be able to produce a single antibody to defend yourself.
What good in any evolutionary sense is that, Doctor? Tell me, please.

If you tried to then make the other chromosome do the site-specific
recombination that these seven immune genes do, you would have
cells producing weird bi-valent antibodies or which has two TcRs,
and after the next generation there would be no untampered set
of genes on either chromosome to produce any antibodies apart
from the bi-valent type you were selecting in that one cell. That is
not what happens in real life Dr. Pitman, and you *should* know.
You do understand "allelic exclusion", right? And cloning, right?

Tell me... tell the Good Lurkers and all of Talk.Origins, just how
you can say "evolution happens" here when it just doesn't at all.

Is that where the Designers brings in all that new code, to replace
the bits that the lymphocytes have lost? (Do I need to cite a paper
for you that proves those bits existed and were cut out?)

> For example, it is pretty much the same thing as Dawkins did with his
> "Methinks it is like a weasel" evolution algorithm. The offspring of a
> completely random sequence that produced a single position with a
> closer match to "Methinks . . ." were preferentially chosen out and
> given increased reproductive advantages over their peers. And, because
> of this, over just a few generations the exact phrase "Methinks it is
> like a weasel" quickly evolved.
>
> Exactly the same thing happens with antibody evolution. Each
> generation of immune cells produces a range of variations of
> antibodies. Those cells that produce just a little better match are
> preferentially chosen out from among their peers to receive a
> reproductive advantage. Very quickly, antigen specificity is improved
> over time.

That *is* a feature of the immune system, but it does not change
the genes in the eventual offspring, there are no changes in the
gene pool with respect to the binding pockets of antibodies or
of the T-cell receptors (which control antibody production on a
basis of similar genetic effect). There is "evolution of an immune
response" in an individual. That is evolution (but only of immunity).
It is not evolution of a species.

It differs from one individual to another and the features are not
passed on in the sperm or egg to another generation in any form
that can be seen to be inherited. It is *not* evolution (of a species).

There are no changes in the gene pool from alterations in an antibody
binding site via somatic hypermutation (run the terms "somatic" and
"hypermutation" together in PubMed - 1136 hits, 233 reviews... see
"Targeting of somatic hypermutation." Nat Rev Immunol. 2006
Aug;6(8):573-83. PMID: 16868548 for a recent review from nature NRI.)

A PubMed search with "somatic hypermutation evolution" gives 92 hits.
Read them. Read them *all* and tell me which one shows how species
changes occur from changes in an antibody response.

(Hint - they don't. There are no effects from hypermutation in
evolution, and there are not even possible effects except perhaps
via templates of antibodies in breast milk forming anti-idiotypes
and anti-anti-idiotypes in the offspring, but that is more Lamarckian
than Darwinian anyway and you have to invoke Jerne's network
hypothesis to even talk about this stuff. There is even a paper to
cite for you here, not that you'll read it: "Lamarckian inheritance
by somatically acquired maternal IgG phenotypes" Trends Immunol.
2004 Apr;25(4):180-6. Review. No abstract available. PMID: 15039044)

(Isn't that great - I fire off a blast of true immunobiology theory,
the sort my boss likes to keep me around for, and PubMed has
a T.I. paper just two years old that will no doubt back me 100%.
Damn. I really should go somewhere to teach Immunology so more
medical students don't turn out as confused as our Dr. Pitman here.)

> While I would accept this as real evolution in action, unlike Marc, it
> is template-based evolution. Not all types of functions can be built
> up in this manner. For example, how would a flagellar motility system
> be build using a template? There simply is no template upon which
> every single residue position change can be selected as an improvement
> or a deterioration of the flagellar motility function. Flagellar
> motility simply can't be realized in any incremental degree until a
> very large number of residues are correctly arranged to begin with.
> Obtaining this minimum requirement can only be done via an extensive
> random walk through a host of non-beneficial options - from any
> starting point a non-flagellate genome may have.
>
> > Your body can in a span of a few weeks produce an antibody to almost
> > any foreign protein. Real time protein evolution in that the
> > resulting antibody will contain sequences that are different from
> > anything in your germ line.
>
> That's true, but it's all based on template matching . . .

Only in the B-cells, and only in the course of an immune response.

........... snp

> > Oh, and did your designer leave any other "traces" besides the
> > bacterial flagella? It seems to the only specified example you toss
> > out.
>
> Translation, transcription, pinocytosis, basic vision systems, vascular
> systems, ATP synthesis, etc. Every living thing requires very
> high-level systems of function in order to exist - none of which can be
> produced by random mutation and function-based selection. They simply
> aren't template based.

Templates have nothing to do with this. Have you considered that
maybe you should read a few of the "just so" peer-reviewed stories
that I have suggested to you recently? To actually read them for real
comprehension? It might do you a world of good, since you are
so totally wrong so often about so much of this.

Someday you might realize how wrong you are about the immune
system and also about evolution of that system (I'll address that
later) and then you might just wake up to the fact that you are
wrong about each and every system you were thinking about in
the passage above, about the ones you named (I really liked your
"basic vision systems" one) and you are even wrong about the other
ones that you didn't list there, Dr. Pitman. Flat-out mistaken and
completely off base about complexity and evolution throughout.

Of course, since you must be super-trolling, it's what you have to do.

(signed) marc

z

unread,

Aug 25, 2006, 3:49:35 AM8/25/06

On 23 Aug 2006 09:08:30 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

Actually, I'm not sure that has been rigorously tested whether or not
you can just turn on all the genes for the structural proteins at
once. Obviously you can turn half on, wait till they are done, and
then turn the other half on without any problems.

From an energetic standpoint it does make sence to split the process
up this way. You need part of the motor and the hook to make the T3SS
to actually get the flagellar whip out there. Finishing the motor
before you have something to spin would waste energy. Making the
flagellar subunits before they have something to attach too is risky
as polymerization in the cytosol would be dangerous.

Only if you require selection to act all at once. Cooption is the
most likely route to getting to a flagella.

If you are refering to protein templates, you are way off base here.
Antibodies are semi-randomlly made- there are a huge number of
potential sequences possible for the CDR's, but it is non-infinite.
Something on the order of 10^20 theoretically, with about 10^12 or so
actually used.

There is no such thing as a "pre-established non-self antigen", and
you will make self-reactive antibodies all the time. In a very simple
sense, self-reactive B cells are spanked on the nose and not given a
cookie. The eventually die (mostly- autoimmune disaases are the main
exception). B cells that do respond to a foreign antigen AND don't
respond to self are given a cookie and undergo a process (in mammals)
of what is known as somatic hypermutation. They actually mutagenize
their recombined antibody genes.

However, there is no guidence to the initial recombination events that
determine whether or not a B cell makes an antibody that rocognizes a
target. If that doen't happen, then bad things might happen. Then
again, the innate and/or cell mediated bits of the immune system do a
pretty fair job.

>
>For example, it is pretty much the same thing as Dawkins did with his
>"Methinks it is like a weasel" evolution algorithm. The offspring of a
>completely random sequence that produced a single position with a
>closer match to "Methinks . . ." were preferentially chosen out and
>given increased reproductive advantages over their peers. And, because
>of this, over just a few generations the exact phrase "Methinks it is
>like a weasel" quickly evolved.
>
>Exactly the same thing happens with antibody evolution. Each
>generation of immune cells produces a range of variations of
>antibodies. Those cells that produce just a little better match are
>preferentially chosen out from among their peers to receive a
>reproductive advantage. Very quickly, antigen specificity is improved
>over time.

If you use your models, this would be impossible. Does this suggest
you need to revise your models?

>
>While I would accept this as real evolution in action, unlike Marc, it
>is template-based evolution. Not all types of functions can be built
>up in this manner. For example, how would a flagellar motility system
>be build using a template? There simply is no template upon which
>every single residue position change can be selected as an improvement
>or a deterioration of the flagellar motility function. Flagellar
>motility simply can't be realized in any incremental degree until a
>very large number of residues are correctly arranged to begin with.
>Obtaining this minimum requirement can only be done via an extensive
>random walk through a host of non-beneficial options - from any
>starting point a non-flagellate genome may have.

Again, your assumption is that the flagella had to "poof" all in one
selection event.

>> Your body can in a span of a few weeks produce an antibody to almost
>> any foreign protein. Real time protein evolution in that the
>> resulting antibody will contain sequences that are different from
>> anything in your germ line.
>
>That's true, but it's all based on template matching . . .

The selection is at the anigen-antibody level. So when does
protein-protein interaction deviate from "template matching" from your
definition.

>
>> Protein-protein interactions are easy to evolve. While ther are
>> examples of proteins that actually swap bits of secondary structure to
>> form quaternary structure, for the most part it's just two surfaces
>> sticking together. You fixate on this as if it's a big deal-
>> something that caused me to scratch my head and wonder why. Getting a
>> protein to recognize a small moleule and actually do something with it
>> is far trickier.
>
>For a single protein - yes. However, when you starting talking about
>dozens of specific proteins needing to stick to each other in very
>specific ways, the statistics involved start really adding up. We
>aren't just talking about simply getting one protein to stick to
>another in just any old way. We are talking about dozens of proteins
>sticking to each other in a very specific way that cannot be built up,
>one tiny residue change at a time, via template-type matching.

Well, practically speaking, you are talking about a structure that is
made up of roughly a dozen proteins. Most of the protein-protein
interactions in that structure are self-interactions. There are
critical non-self interactions involved but it's not as complicated as
you make it out.

>
>> >> We have fairly large datasets now. It's very clear that there are a
>> >> smallish numeber (say ~100) of protein folds that are found commonly
>> >> in biological systems. And its quite clear that they can be very
>> >> divergent in sequence and still have the same 3D structure.
>> >
>> >That's also true. However, when it comes to higher and higher levels
>> >of minimum system requirements the non-beneficial ways in which these
>> >"smallish" number of folds can be arranged relative to each other
>> >increases exponentially faster than the very small number of ways that
>> >will actually work to perform a given function - like flagellar
>> >motility.
>>
>> Expectations are everything. If you expect that you can get a fully
>> functionally flagellar motility system all in one go, sure you'd be
>> disappointed. The cooption of other prexisiting simpler systems has
>> been presented and ignored by you so I won't elaborate further.
>
>Where have you or anyone else shown that the simpler subsystems you
>proposed can be easily stuck together in just the right way to reach
>the next beneficial steppingstone function in your proposed pathway
>with just a handful of residue changes? You make these bald claims
>that such a detailed description has been delivered, but this is just
>hot air. Where is this description? I have yet to read anything of
>the sort.

Evolution does not plan for the future and bacteria don't make genome
back-ups for us to look over. We do have examples of cooption in your
favored system. The T3SS of some eubacterial parasites of eukaryotes
is either A) a cooption with specialization from the flagellare T3SS
or B) an evolutionary relic of an independant system that was coopted
by the flagella. A parses best given the restricted range of
organisms that we have noted it in. The caveat is that the range of
organisms that his been observed in are organisms are of special
interest because they are pathogens.

Tranlsation is a good one in that it's the system that shares the most
commonality between all three kingdoms AND is the ugliest one to work
with from a biochemical POV. Trascription - bring on your examples.
Pinocytosis is laughably easy mechanically. Basic vision systems are
also easy, but non-essential. Vascular systems- plants or animals?
Gonna be hugelly different, and I don't know much about plants, ATP
synthesis can be done a bazillion different ways- are you asking why
ATP?

B Miller

Seanpit

unread,

Aug 25, 2006, 6:17:37 PM8/25/06

r norman wrote:

> >> It is your claim
> >> that consecutive elements in a nucleotide sequence or an amino acid
> >> sequence are independent that is wrong. That is true whether or not
> >> there is a specific order to the sequence.
> >
> >You are quite mistaken Richard. Each position in a sequence of
> >nucleotides and amino acids is indeed independent as a truly random
> >mutation could change any position to another character in a truly
> >random way. That is the basis of evolutionary theory. Mutations have
> >to be non-directed and truly random. Natural selection is supposed to
> >be the non-random force here - not mutations.
>
> You are exposing ever more ignorance of probability theory. Just
> because successive events are correlated does not mean that a process
> is not "random".

Successive mutations are not correlated with previous mutations. They
are pretty much independent of each other.

> Just because the possibilities in a random process
> are not uniformly distributed, every outcome being equally likely,
> does not mean that the process is not random.

I never said otherwise. What I said was that random genetic mutations
are pretty much independent random events. You see, Richard, mutations
are both random and independent. They are not generally biased by
prior events.

> There are substitution mutations that do seem to be quite independent
> events, although not every substitution is equally likely nor is the
> probability of mutation the same at all sites.

As a general rule, substitution or point mutations are pretty much
independent random events. There are mutational hot spots, but by in
large, point mutations are independent events.

> Still, one mutation is
> independent of another. There are other mutations where snippets of
> DNA are repeated or deleted or moved to another location or inverted.

That's true, and these types of mutations are also independent events
- independent of what came before or what may come after.

> In this case, what happens at one site is not at all independent of
> what happens at the adjacent site. That is why we talk of protein

> "motifs" and "gene families".

There certainly are protein or gene motif and families, but this has
nothing to do with the fact that the mutations that affect DNA are in
fact largely independent events. Just because a mutation may affect
multiple characters at the same time does not make it a dependent
event.

> The occurrence of a specific mutation
> affecting a particular character or trait does not seem to be
> associated with any aspect of that trait so that mutations are not
> "directed" in a particular direction with regard to the final outcome.

Unless a mutation ends up producing a functionally neutral change,
mutations may indeed affect the functional aspects of a functional
trait.

> That does not mean that every single nucleotide is completely
> independent of every other nucleotide in every possible mutation.

The mutations themselves are independent events. The nucleotides that
get changes may in fact be changed independently by mutations. The
fact that many or just one may be changed at the same time does not
change the fact that the mutations themselves are in fact independent
events. The odds of finding a novel beneficial functional sequence via
mutations are still the same - regardless of if you use a random walk
of sequential point mutations or random selection of multicharacter
mutations as you search through sequence space. The odds of success
are pretty much the same.

> There are also interesting complications involving mutational "hot
> spots" which seem to be much more easily modified plus environmental
> situations that cause cell biochemical changes that influence the
> effectiveness of DNA error detection and repair mechanisms.

Yes, that is true. But, none of this improves the odds of finding
novel beneficial functional sequences.

> No, the
> actual occurrence of mutations is not at all the same as successive
> flips of an unbiased coin determining nucleotide sequences. But you
> are not likely to accept any of this, either.

Not true. The odds of actual mutations landing on a specific target
sequence is very much the same as flipping coins or rolling one or
multiple dice. There simply is no fundamental difference.

Sean Pitman
www.DetectingDesign.com

Perplexed in Peoria

unread,

Aug 25, 2006, 7:08:00 PM8/25/06

"Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1156201518.4...@m79g2000cwm.googlegroups.com...

Yep. You got it exactly.

> Of course, I've argued that gene duplication does not make novel
> starting points. It only makes more of the same starting point. You
> are still left with having to cross a gap that includes all potential
> sequences - even the ones that won't fold to make much of anything.
> This might be taken to mean that the random walk/sampling required is
> not significantly reduced.

But there aren't gaps - whole impassable channels - composed of
sequences that won't fold. Sewell Wright has confused generations
with his metaphor of a 'fitness landscape'. Read the recent book
by Sergei Gavrilets and reset your intuitions on this point.

What you seem to be suggesting is that gene duplication does nothing
more than add more paper. The writing on that paper is totally
useless in terms of producing another page for 'the book' by mutation
and natural selection. The paper might as well have been blank to
begin with. Just not so. The page contains whole words which merely
need to be rearranged to form whole new sentences.

> Unless, unless of course the genome already has the needed part to make
> the next step in the genome pre-formed. Your argument seems to suggest
> that the odds that this will in fact be the case are pretty good! -
> since many of the non-workable potential sequences are screened out
> ahead of time by default. And, this is in fact true at lower levels of
> functional complexity. However, at higher and higher levels, the size
> of the step to the next novel function grows linearly. It becomes
> harder and harder to find a pre-existing sequence that would cross this
> step in one fell swoop with one single mutation event - such as a
> duplication and insertion of just the right sequence into the correct
> spot. The problem is that the odds that the needed sequence that would
> fill the gap actually exists preformed in the same genome decrease
> exponentially as well with each step up the ladder.

I think that Dawkins's "weasel' game has misled you into how evolution
actually works. Either that, or you have been misled by that "in His
image and likeness" thing. There is no predetermined end point to
be reached. Instead there is a lot of stumbling around as proteins
first take one role all the time (doing X, say), then gradually are
modified to do X only if Y is present in the environment (call it Y -> X)
and then further mutate into something like (X -> ~Y). It is not
a straight line path from something that doesn't work properly to
something that does.

> If you want to use a specific example, please do explain a specific
> functionally beneficial step in the evolution of the flagellar system
> from some proto form.

I'm pretty sure that one has already been sketched - for example,
at the t.o. website.

> Or, provide any actual experimental
> demonstration of the evolution of any new function that require more
> than a few thousand fairly specified bp of DNA.

Hmmm. Let's see. That would require that I bio-engineer something
like (say) 4000 different strains of bacteria - each containing
proto-flagelar proteins doing something useful, with the first not
having anything like a flagellum and the last with a fully functional
flagellum. And when I line up these 4000 petri dishes in a row,
each differs from its predecessor by only a single mutation. Is
that what you are asking for?

Well, I'm an armchair sort of 'scientist'. I don't have the technical
expertise to make that demonstration. But you are welcome to try
the counter-demonstration. As I understand it, that would involve
some 4^4000 petri dishes plus experiments showing that every path
from starting point to end point sinks you deep into a fitness
'channel' at some point.

Not interested in trying that? Well, I guess we will have to
just snipe at each other from armchairs then. But I hope I have
given some sense of why your sniping isn't convincing anyone.

And I think that you are trying to scale "methinks it is a weasel" up
to a monkey typing "Hamlet". Evolution just doesn't work that way.

> > We can talk about abiogenesis some other day. You
> > can even talk some more about cilia and flagella.
> > I certainly haven't completely explained them here.
> > All I have done is to show that simple multiplication
> > of probabilities is not the way to approach these
> > kinds of evolved 'IC'.
>
> I really don't think you've done what you think you've done at all.
> The islands of potentially beneficial sequences simply become more and
> more stretched out at higher and higher levels of functional complexity
> until the bridges between them simply snap apart and they become truly
> isolated in a very remote way. Now, no single multicharacter
> insertion/deletion/translocation etc is going to get you there.
> Multiple mutations involving multiple characters each are required.
> And, multiplication of the odds is back . . . and at very low levels.

It must be very frustrating for you when knowlegeable people don't
share your intuitions. Hell, I know it is. It is frustrating to
me in the abiogenesis field where everyone else seems to be stuck
on "First you create the building blocks, then you join the blocks
together".

Seanpit

unread,

Aug 25, 2006, 7:10:40 PM8/25/06

Marc wrote:

< snip >

> > Exactly the same thing happens with antibody evolution. Each
> > generation of immune cells produces a range of variations of
> > antibodies. Those cells that produce just a little better match are
> > preferentially chosen out from among their peers to receive a
> > reproductive advantage. Very quickly, antigen specificity is improved
> > over time.
>
> That *is* a feature of the immune system, but it does not change
> the genes in the eventual offspring, there are no changes in the
> gene pool with respect to the binding pockets of antibodies or
> of the T-cell receptors (which control antibody production on a
> basis of similar genetic effect). There is "evolution of an immune
> response" in an individual. That is evolution (but only of immunity).
> It is not evolution of a species.

I'm not talking about evolution of the species here. I'm only
interested in the evolution of functions here. I don't care if the
evolved function is passed on to the species offspring or not. I only
care if it passed on to the offspring of some kind. In this case, the
"offspring" are the immune system cells.

> It differs from one individual to another and the features are not
> passed on in the sperm or egg to another generation in any form
> that can be seen to be inherited. It is *not* evolution (of a species).

But, as you yourself said, it *is* evolution of the immune system
function within a particular individual. This is still Darwinian-style
evolution in that a population, a population of immune cells, evolves
improved antibody-antigen specificity over a few generations of immune
cells. You have everything you need. You have a population that
undergoes random mutations that affect functional aspects of that
population and passes these changes on, in a selectable manner, to
their offspring. It is the evolution of a population within an
individual. It still counts as evolution even though the individual
can't pass the information on to his/her own offspring.

< snip rest >

> (signed) marc

Sean Pitman
www.DectectingDesign.com

r norman

unread,

Aug 25, 2006, 7:15:17 PM8/25/06

On 25 Aug 2006 15:17:37 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

>Not true. The odds of actual mutations landing on a specific target
>sequence is very much the same as flipping coins or rolling one or
>multiple dice. There simply is no fundamental difference.
>

What is a "specific" target sequence. This is an enormous error on
your calculations, the notion that because evolution happened to
produce a specific sequence in its operation, then evolution must be
demonstrated to produce exactly that sequence or else it must be
rejected.

It is certain that the evolutionary process will result in "some"
nucleotide sequence being produced and that each protein involved in
some operation will have "some" amino acid sequence. It is also
certain that shuffling a deck of cards will result in "some" sequence
being produced. Why do you suspect that that one sequence is the only
one that is possible or reasonable or is the "goal" of evolution? All
that is necessary is that it produce a sequence that works.

Seanpit

unread,

Aug 26, 2006, 12:53:13 AM8/26/06

Von R. Smith wrote:

< snip >

> > > On the other hand, when trying to play up the complexity of the

> > > flagellum, he will point out that one needs all of the 20-odd
> > > structural proteins, plus the supporting cast of chaperones, transport
> > > proteins, etc., for it to work.
> >
> > That's not all. Not only does a flagellar system need all of its
> > parts, it needs all of its parts to be specifically arranged with each
> > other in three dimensions.
>
> ...and I am still waiting for you to describe the constraints on
> *sequence* variability that this imposes.

How is it wrong to suggest that the underlying code has to be just as
specified as the specificity limitations of the final product?

> > > Sean won't address (or even
> > > acknowledge unless pointed out) the fact that sub-components of the
> > > flagellum have recognizable independent uses, or that most of the
> > > individual proteins have identifiable non-flagellar homologs, or that
> > > one can propose plausible independent functions for the ancestors of
> > > those proteins.
> >
> > This is a deliberate lie. I have addressed this point extensively both
> > in this forum and on my website.
>
> As with the word "explain", you and I apparently have rather different
> notions of what it means to "address" an issue.

You know that I do recognize the fact that sub-components of the
flagellar motility system do in fact carry independent useful
functions. You yourself realize that I've recognized this for a long
time now. Therefore, how is it anything but a deliberate
misrepresentation on your part to say otherwise?

> > Of course the flagellar system is
> > made up of subsystems that do or may have plausible independent
> > usefulness. I've never said otherwise and you know it. Why present
> > this strawman to misrepresent my position in such a deliberate way?
>
> Your behavior here bears out my characterization of it to a tee: "Sean
> will disown his strawman thrice before the cock crows if he's called on
> it".

I disown such statements because I've never made such statements Von.
Why make up stuff like this? Don't you have any real argument?

> As for your slippling it right back into the discussion as soon as you
> find it opportune, here is an example from this very thread since I
> posted the above:
>
> quote
> [z wrote:]
>
> > Protein-protein interactions are easy to evolve. While ther are
> > examples of proteins that actually swap bits of secondary structure to
> > form quaternary structure, for the most part it's just two surfaces
> > sticking together. You fixate on this as if it's a big deal-
> > something that caused me to scratch my head and wonder why. Getting a
> > protein to recognize a small moleule and actually do something with it
> > is far trickier.
>
> [and you responded:]
>
> For a single protein - yes. However, when you starting talking about
> dozens of specific proteins needing to stick to each other in very
> specific ways, the statistics involved start really adding up.
>
> end quote
>
> The only way that "the statistics involved start really adding up" is
> if evolution of the function in question must evolve via your strawman.

I've not made a strawman to misrepresent your own views on how
evolution is supposed to work. I present your views quite accurately.
I just disagree with your notions that evolution could work the way you
suggest. My disagreement with your notions concerning the potential of
evolution isn't a strawman because a strawman argument is not defined
by disagreeing with another's views. It is defined by deliberately
misrepresenting another's views.

Look up the definition of a strawman argument . . .

> If the steps were individually selectable, then the involvement of a
> dozen or more proteins would not be a real problem for evolution.

That's quite true, as I've pointed out myself many many times. The
problem is that the individual steps start becoming bigger and bigger
at higher and higher levels. The size of the step that used to result
in a new beneficial function at lower levels no longer does the trick.
Now, instead of crossing a gap of just one or two residue differences,
a gap of dozens of residues differences must be overcome.

> But
> here as in so many other posts you fail to note that distinction;
> rather, you argue from the unstated assumption that a function
> involving interactions among many different proteins must hit upon all
> those interactions at once.

I've never said this. In fact, I've specifically stated the opposite
many many times - directly to you. The fact that you continue to
present this notion as representative of my position is no less than a
deliberate misrepresentation on your part.

For example, the evolutionary pathway of a flagellar motility system
need not evolve all the parts of the flagellar motility system all at
once. Certainly not. There are definitely steppingstone functions
along the pathway that would yield benefits before reaching the final
flagellar motility system. However, these stepping stones are,
individually, too far apart to reach any one of them from any other.
That's the problem. It isn't that just the flagellar motility system
cannot be evolved. It is that none of the steppingstones in the pathway
can be evolved. That's the problem.

> Likewise, this strawman seems to be the
> unacknowledged basis for your whole "four 6s in a row" vs. "two pairs
> of two 6s" analogy; again, you are trying to suggest that the proteins
> in a function with a "3D requirement" must come into existence all at
> once, rather than appear gradually. If you disagree, then tell me what
> else your "four 6s in a row" actually refers to.

The four 6s in a row represents the demands of the system in question.
It represents the rarity of a specific sequence requirement in sequence
space. This does not mean, however, that a function that requires just
two or even three 6s in a row couldn't be useful in a given "genome".
Of course, this would mean that a bunch of double and triple 6s would
be all over the place. And, of course, this would mean that it would
be quite a bit easier to realize the four 6s in a row. However, the
function that requires that four sixes be in a row still requires that
four 6s be in a row. That function is still quite rare in sequence
space - exponentially rarer than the function that requires two double
sixes.

Do you understand the difference here now? The minimum part
requirement for a function doesn't mean that there are no intermediate
steps that are also functionally beneficial. It just means that its
own function requires a specific type of sequence and that specificity
and minimum size translates into rarity within sequence space.

< snip >

> > You may say that my views are wrong here, but you really can't say that
> > I'm building a strawman to misrepresent your true position - unless you
> > don't understand the definition of a strawman argument (aka Howard
> > Hershey)
>
> I do not think you are in any position to fault other people's grasp or
> use of terms. The accusation of a strawman rests upon your repeated
> use of it as your model for what the evolution of complex structures
> and functions entails. Once it is pointed out that you are *not*
> entitled to assume that evolution of complex functions must proceed by
> your strawman version of it, all that is left of your argument is bare
> incredulity and rejection.

You can argue that my model isn't correct, but you cannot argue that
I'm using a strawman argument to misrepresent your position Von. A
strawman argument is a misrepresentation of another's position in order
to attack a weaker non-real version of an opponent's views. I've not
done this. I've not misrepresented your own position - your actual
views. I've presented your views correctly. I've just presented my
own views, as my own, not calling them your views. You may disagree
with my views on how evolution would have to work, but they are by no
means labeled by me as your views. They aren't your views. They are my
views. By definition then I'm not building a strawman
misrepresentation of your views.

Look up the definition of a strawman Von. You really are misusing the
term.

> > > The
> > > only excuse I have seen him give for steadfastly
> > > ignoring "our" version of evolution in any of his calculations of how
> > > long is the failure of scientists to demonstrate any real-time examples
> > > of any of the hypothetical intermediate evolutionary steps. (There are
> > > such examples, but he has excuses to cover those, too.)
> >
> > Where are these examples Von? Where has anyone set up one of your
> > non-flagellate protosystems and shown them to merge together to form
> > any subsequent step in your proposed pathway?
>
> I have already given you examples, in fact Matzke alludes to two of
> them himself in his article: the evolution of elective suppression of
> pilus-terminal adhesins to facilitate random dispersal, and changes in
> the shape and size of the hook and filament to make it more optimal for
> motility.

Making a function work better is not the same thing as the evolution of
a new type of function to begin with. Once flagellar motility is in
place, to at least a slight degree of selective advantage, further
modifications and improvements of that function will most certainly be
easily achieved - rapidly. For example, once a bacterial colony has
evolved the lactase function to at least a slight advantage, it can
increase the level of lactase function over time very quickly.
However, until it achieves at least some level of useable lactase
function, there is no way to build the lactase function via small steps
over time - because of the gap problem.

So no. The optimization of the shape or size of a hook and/or filament
to make for more optimal motility is not the evolution of a new type of
function. It is only the modification of the same function.

> Howard Hershey also gives examples of re-evolving the
> protein-protein interactions between fliF and fliG. I pointed these
> out to you on at least two other occasions, and you have never
> commented, at least not in response to me.

And this is like messing a pre-existing system up by throwing one tiny
mutation into the works and then reversing the damage done with one
tiny reverse mutation. Give me a break! I'm just amazed by the stuff
you and Howard come up with in order to try to avoid the main issue.
Do you know that cavefish that do not grow eyes anymore have a single
point mutation that causes this lack of eye growth? If placed back in
a lighted environment, their offspring quickly evolve their eyes back
again because this single point mutation is relatively easy to reverse.

Demonstrating that it is easy to move one tiny step off an island of
beneficial function, and then back on the island with one tiny reverse
step, is not the same thing as demonstrating that it was easy to find
the island starting from any other island to begin with.

> > You're just making this stuff up as you go along - hoping that mere
> > bluster will be good enough to prop up your baseless position . . .
>
> Project much?

Where is your evidence Von? That's all I'm asking for. What have you
actually brought to the table? What do the "evidences" you've just
listed here really amount to but so much hot air?

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 26, 2006, 3:58:32 AM8/26/06

r norman wrote:
> On 25 Aug 2006 15:17:37 -0700, "Seanpit"
> <seanpi...@naturalselection.0catch.com> wrote:
>
>
> >Not true. The odds of actual mutations landing on a specific target
> >sequence is very much the same as flipping coins or rolling one or
> >multiple dice. There simply is no fundamental difference.
>
> What is a "specific" target sequence.

A target sequence is any sequence that happens to support a new
beneficial function.

> This is an enormous error on
> your calculations, the notion that because evolution happened to
> produce a specific sequence in its operation, then evolution must be
> demonstrated to produce exactly that sequence or else it must be
> rejected.

I never said that evolution must produce one and only one sequence or
be rejected. What I said was that evolution must come up with sequences
that result in beneficial functions. Evolution actually does this at
very low levels of functional complexity, because the ratio of
sequences in sequence space that are potentially beneficial vs. the
ones that are not is quite high. However, with each additional size
and specificity requirement this ratio of potentially beneficial vs.
non-beneficial declines in an exponential manner. This makes the odds
of a random mutation of any kind, point mutation or otherwise, more and
more unlikely to hit on any sequence in sequence space with new
attached beneficial function.

> It is certain that the evolutionary process will result in "some"
> nucleotide sequence being produced and that each protein involved in
> some operation will have "some" amino acid sequence.

That's true. But, the majority of mutations that end up producing
different residue sequences are not beneficial, but detrimental - even
at very low levels of functional complexity. As you move up the
ladder, this ratio becomes smaller and smaller and smaller - in an
exponential manner.

> It is also
> certain that shuffling a deck of cards will result in "some" sequence
> being produced.

Yep . . . but not just any sequence will produce something that is
*beneficial*. That's the key concept here.

> Why do you suspect that that one sequence is the only
> one that is possible or reasonable or is the "goal" of evolution? All
> that is necessary is that it produce a sequence that works.

Yes, and finding any sequence that "works" as a new and beneficial
function becomes exponentially harder and harder to do when you start
talking about functions that require greater minimum sizes and
specificity minimums.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 26, 2006, 4:55:59 AM8/26/06

z wrote:

< snip >

> >> You miss the point. There is a huge amount of structural information
> >> required to "specify" an enzymatic cascade. The active site of each
> >> enzyme must recognize both the substrate and the product of the
> >> reaction.
> >
> >That's true. Each individual enzyme in a cascade may indeed require a
> >great deal of specific order to its individual residues relative to
> >themselves within that enzyme. However, the overall function of the
> >enzymatic cascade does not require the additional requirement that each
> >individual enzyme be specifically arranged in 3D space relative to all
> >the other enzymes. A flagellar motility system does have this
> >additional specificity requirement - which makes an exponential
> >difference in the rarity of such a system in the potential of sequence
> >space.
>
> Only if you require selection to act all at once. Cooption is the
> most likely route to getting to a flagella.

It doesn't matter how you get there, the final result, the flagellar
motility system, requires a rather large minimum part and specificity
requirement. It doesn't matter if you got there by co-opting previous
systems via evolutionary mechanisms or straight up de novo intelligent
design. The final product requires a minimum number of residues to be
arranged in a pretty specific way.

This is not true of an enzymatic cascade. No matter how such a cascade
is created, it does not require that all of its individual protein
parts, no matter how much they are individually specified, to be
specifically arranged relative to each other. This creates an
exponential difference in rarity within sequence space in comparison
with a flagellar motility system - the odds of obtaining all the needed
parts in the proper order.

Again, for example, it is much much easier to throw two double sixes
compared to throwing two double sixes in a row.

> >You need to talk to Marc about antibody evolution. Marc says that
> >antibody evolution doesn't count as real evolution. But, that is Marc
> >for you. Personally, I agree with you that improvement in antibody
> >specificity over time, via random mutation and function-based
> >selection, is indeed real evolution in action. However, there is just
> >one little problem with this sort of evolution.
> >
> >The problem with antibody evolution is that it is template-based. All
> >that has to happen is for a very small change in the antibody sequence
> >to result in a better match to a pre-established non-self antigen
> >sequence for a selective advantage to be realized. The odds of an
> >improved binding match to a pre-established template being realized are
> >actually quite good.
>
> If you are refering to protein templates, you are way off base here.
> Antibodies are semi-randomlly made- there are a huge number of
> potential sequences possible for the CDR's, but it is non-infinite.
> Something on the order of 10^20 theoretically, with about 10^12 or so
> actually used.

There certainly are a large number of pre-formed antibody sequences
before the virgin immune system is ever exposed to a foreign antigen.

> There is no such thing as a "pre-established non-self antigen",

Any foreign antigen that enters the immune system is pre-established
before it meets the immune system. The immune system is able to
respond with greater force and specificity against the same antigen
with repeated exposure.

> and
> you will make self-reactive antibodies all the time. In a very simple
> sense, self-reactive B cells are spanked on the nose and not given a
> cookie. The eventually die (mostly- autoimmune disaases are the main
> exception). B cells that do respond to a foreign antigen AND don't
> respond to self are given a cookie and undergo a process (in mammals)
> of what is known as somatic hypermutation. They actually mutagenize
> their recombined antibody genes.

That's right . . .

> However, there is no guidence to the initial recombination events that

> determine whether or not a B cell makes an antibody that rocognizes a
> target.

Correct . . .

> If that doen't happen, then bad things might happen. Then
> again, the innate and/or cell mediated bits of the immune system do a
> pretty fair job.

Against certain types of invaders . . .

> >For example, it is pretty much the same thing as Dawkins did with his
> >"Methinks it is like a weasel" evolution algorithm. The offspring of a
> >completely random sequence that produced a single position with a
> >closer match to "Methinks . . ." were preferentially chosen out and
> >given increased reproductive advantages over their peers. And, because
> >of this, over just a few generations the exact phrase "Methinks it is
> >like a weasel" quickly evolved.
> >
> >Exactly the same thing happens with antibody evolution. Each
> >generation of immune cells produces a range of variations of
> >antibodies. Those cells that produce just a little better match are
> >preferentially chosen out from among their peers to receive a
> >reproductive advantage. Very quickly, antigen specificity is improved
> >over time.
>
> If you use your models, this would be impossible. Does this suggest
> you need to revise your models?

You evidently don't understand my model very well at all. My model
predicts rapid evolution when the evolution is based on a template
model like this.

The preformed antibodies of the virgin immune system have not undergone
"evolution" yet. The B-cells are simply programmed to cast a wide
general fairly non-specific net of antibody variations. However, once
the immune system is exposed to a foreign antigen the immune system is
able to produce more and more specific antibodies against that foreign
antigen with each generation of immune cells - with the use of random
mutations and function-based selection.

It is just that, in this case, the antigen acts as a template model.
Each small change in the antibody that produces a better fit to the
antigen template is rewarded with increased reproductive fitness. The
changes needed to produce a better fit are very small changes - often
only the difference of a single residue change. Therefore, the ratio
of what will improve the match vs. what won't is actually very high.
That is why this sort of evolution can and does happen very quickly.

Now, compare this with the problem of evolving a function like
flagellar motility. Where is the template here where one or two
residue changes will produce an improvement in flagellar motility
before flagellar motility is even achieved yet? - or any other
beneficial steppingstone function? There simply is no template to base
such small changes on in a selectable way. That's the problem.
Antibody-antigen matching evolution is like Dawkins' "Methinks it is
like a weasel" algorithm. Flagellar evolution cannot work like this.

> >While I would accept this as real evolution in action, unlike Marc, it
> >is template-based evolution. Not all types of functions can be built
> >up in this manner. For example, how would a flagellar motility system
> >be build using a template? There simply is no template upon which
> >every single residue position change can be selected as an improvement
> >or a deterioration of the flagellar motility function. Flagellar
> >motility simply can't be realized in any incremental degree until a
> >very large number of residues are correctly arranged to begin with.
> >Obtaining this minimum requirement can only be done via an extensive
> >random walk through a host of non-beneficial options - from any
> >starting point a non-flagellate genome may have.
>
> Again, your assumption is that the flagella had to "poof" all in one
> selection event.

Not true. There are certainly many potential steppingstone functions
that could produce a series of beneficial functions along the way.
However, my position is that these steppingstone functions are too
widely separated from each other in sequence space. Too many changes
would be required to go from one to the next in the flagellar evolution
pathway. You simply can't get there by changing one or two residues in
one or the other of two pre-existing subsystems to produce a united
system with a new beneficial function. The changes that would be
required involve many dozens of residues to step between every single
steppingstone in the pathway. Even one such gap cannot be crossed by
random mutations of any kind. Natural selection is not helpful in the
crossing of such a gap because, until the gap between one beneficial
steppingstone and the next is crossed by purely random mutations,
nature has nothing to do but keep what it already has as beneficial in
good working order. It can't select, in a positive way, a beneficial
sequence that hasn't yet been discovered by random mutations.

> >> Your body can in a span of a few weeks produce an antibody to almost
> >> any foreign protein. Real time protein evolution in that the
> >> resulting antibody will contain sequences that are different from
> >> anything in your germ line.
> >
> >That's true, but it's all based on template matching . . .
>
> The selection is at the anigen-antibody level. So when does
> protein-protein interaction deviate from "template matching" from your
> definition.

The ratios are very different. The ratios are very high for an
antibody to match better with an antigen. The ratios are much much
lower for matching a proto-subsystem to another subsystem to produce a
flagellar motility system. First off, the antibody already binds to
the antigen in a selectable way to begin with. The only thing that
"evolves" in this case is an improvement to the same binding function.
It is easy to improve a function once you already have it. It is quite
another thing to evolve the function to begin with when you don't have
it at all.

> >> Protein-protein interactions are easy to evolve. While ther are
> >> examples of proteins that actually swap bits of secondary structure to
> >> form quaternary structure, for the most part it's just two surfaces
> >> sticking together. You fixate on this as if it's a big deal-
> >> something that caused me to scratch my head and wonder why. Getting a
> >> protein to recognize a small moleule and actually do something with it
> >> is far trickier.
> >
> >For a single protein - yes. However, when you starting talking about
> >dozens of specific proteins needing to stick to each other in very
> >specific ways, the statistics involved start really adding up. We
> >aren't just talking about simply getting one protein to stick to
> >another in just any old way. We are talking about dozens of proteins
> >sticking to each other in a very specific way that cannot be built up,
> >one tiny residue change at a time, via template-type matching.
>
> Well, practically speaking, you are talking about a structure that is
> made up of roughly a dozen proteins.

The flagellar motility system is made up of a minimum of over 20
proteins - but that is beside the point.

> Most of the protein-protein
> interactions in that structure are self-interactions. There are
> critical non-self interactions involved but it's not as complicated as
> you make it out.

Oh really? The interactions of the 20+ different protein parts isn't
as complicated or "specified" as I make it out? Tell me, which one of
these interactions isn't really needed?

> >Where have you or anyone else shown that the simpler subsystems you
> >proposed can be easily stuck together in just the right way to reach
> >the next beneficial steppingstone function in your proposed pathway
> >with just a handful of residue changes? You make these bald claims
> >that such a detailed description has been delivered, but this is just
> >hot air. Where is this description? I have yet to read anything of
> >the sort.
>
> Evolution does not plan for the future and bacteria don't make genome
> back-ups for us to look over. We do have examples of cooption in your
> favored system. The T3SS of some eubacterial parasites of eukaryotes
> is either A) a cooption with specialization from the flagellare T3SS
> or B) an evolutionary relic of an independant system that was coopted
> by the flagella. A parses best given the restricted range of
> organisms that we have noted it in. The caveat is that the range of
> organisms that his been observed in are organisms are of special
> interest because they are pathogens.

It is strange that the TTSS system is so commonly touted as the most
likely starting point by many evolutionists since the TTSS system is
supposed to have evolved hundreds of millions of years after flagellar
evolution. Many argue that there is good evidence to believe that the
TTSS starting point arose from the fully formed flagellum and not the
other way round.

Consider that the bacterial flagellum is found in both mesophilic,
thermophilic, gram-positive, gram-negative, and spirochete bacteria
while TTSS systems are restricted to a few gram-negative bacteria. Not
only are TTSS systems restricted to gram-negative bacteria, but also to
pathogenic gram-negative bacteria that specifically attack animals and
plants . . . which supposedly evolved billions of years after flagellar
motility had already evolved! Beyond this, when TTSS genes are found
in the chromosomes of bacteria, their GC (guanine/cytosine) content is
typically lower than the GC content of the surrounding genome. Given
the fact that TTSS genes are commonly found on large virulence plasmids
(which can be easily passed around between different bacteria), this is
good evidence for horizontal transfer to explain TTSS gene
distribution. Flagellar genes, on the other hand, are usually split
into 14 or so operons, they are not found on plasmids, and their GC
content is the same as the surrounding genome suggesting that the code
for the flagellum has not been spread around by horizontal transfer.

So, if anything, it seems like the TTSS system would have evolved from
the flagellum (which does in fact contain TTSS system-like subparts,
such as a basal body that secretes various non-flagellar proteins -
including virulence factors), and not vice versa.

Additional evidence for this comes from the fact that the TTSS system
shows little homology with any other bacterial transport system (at
least 4 major ones). Yet, evolution is supposed to build upon what
already exists. Since the TTSS system is the most complex of the
bunch, why didn't it evolve from one of these less complex systems and
therefore maintain some higher degree of homology with at least one of
them? This evidence suggests that the TTSS system did not exist, nor
anything homologous, in the "pre-flagellar era". It must therefore
have arisen from the fully formed flagellum via the removal of
pre-existing parts - and not the other way around. In fact, several
scientists have actually started promoting this idea in recent
literature.

http://www.detectingdesign.com/flagellum.html

> >Translation, transcription, pinocytosis, basic vision systems, vascular
> >systems, ATP synthesis, etc. Every living thing requires very
> >high-level systems of function in order to exist - none of which can be
> >produced by random mutation and function-based selection. They simply
> >aren't template based.
>
> Tranlsation is a good one in that it's the system that shares the most
> commonality between all three kingdoms AND is the ugliest one to work
> with from a biochemical POV.

Ok - show me how it could have evolved? Describe to me what was there
before this function evolved and what it would have taken,
specifically, for this function to evolve.

> Trascription - bring on your examples.

Again, describe to me how the function of transcription could have
evolved. It is very complicated. Please explain to me how such a
complex system could have evolved one little step at a time . . .

> Pinocytosis is laughably easy mechanically.

Oh really? Laughably easy mechanically? Hmmmm . . . please do explain
to me how such a laughably easy system could have evolved - step by
mutational step.

> Basic vision systems are
> also easy, but non-essential.

The most basic vision systems are enormously complex. They are not
anywhere near "easy". Do you have any idea what's involved in order
for the most basic vision function to be realized?

Even a simple light sensitive spot is extremely complicated, involving
a large number of specialized proteins and protein systems. These
proteins and systems are integrated in such a way that if one were
removed, vision would cease.

For example, the first step in vision is the detection of photons. In
order to detect a photon, specialized cells use a molecule called
11-cis-retinal. When a photon of light interacts with this molecule,
it changes its shape almost instantly. It is now called trans-retinal.
This change in shape causes a change in shape of another molecule
called rhodopsin. The new shape of rhodopsin is called metarhodopsin
II. Metarhodopsin II now sticks to another protein called transducin
forcing it to drop an attached molecule called GDP and pick up another
molecule called GTP. The GTP-transducin-metarhodopsin II molecule now
attaches to another protein called phosphodiesterase. When this
happens, phosphodiesterase cleaves molecules called cGMPs. This
cleavage of cGMPs reduces their relative numbers in the cell. This
reduction in cGMP is sensed by an ion channel. This ion channel shuts
off the ability of the sodium ion to enter the cell. This blockage of
sodium entrance into the cell causes an imbalance of charge across the
cell's membrane. This imbalance of charge sends an electrical current
to the brain. The brain then interprets this signal and the result is
called vision. Many other proteins are now needed to convert the
proteins and other molecules just mentioned back to their original
forms so that they can detect another photon of light and signal the
brain. If any one of these proteins or molecules is missing, even in
the simplest eye system, vision will not occur.

The question now of course is, how could such a system evolve
gradually? All the pieces must be in place simultaneously. For
example, what good would it be for an earthworm that has no eyes to
suddenly evolve the protein 11-cis-retinal in a small group or "spot"
of cells on its head? These cells now have the ability to detect
photons, but so what? What benefit is that to the earthworm? Now,
lets say that somehow these cells develop all the needed proteins to
activate an electrical charge across their membranes in response to a
photon of light striking them. So what?! What good is it for them to
be able to establish an electrical gradient across their membranes if
there is no nervous pathway to the worm's minute brain? Now, what if
this pathway did happen to evolve and such a signal could be sent to
the worm's brain. So what?! How is the worm going to know what to do
with this signal? It will have to learn what this signal means.
Learning and interpretation are very complicated processes involving a
great many other proteins in other unique systems. Now the earthworm,
in one lifetime, must evolve the ability to pass on this ability to
interpret vision to its offspring. If it does not pass on this
ability, the offspring must learn as well or vision offers no advantage
to them. All of these wonderful processes need regulation. No
function is beneficial unless it can be regulated (turned off and on).
If the light sensitive cells cannot be turned off once they are turned
on, vision does not occur. This regulatory ability is also very
complicated involving a great many proteins and other molecules... all
of which must be in place initially for vision to be beneficial.

> Vascular systems- plants or animals?

Both . . .

> Gonna be hugelly different, and I don't know much about plants,

Both are at a fairly high level of functional complexity.

> ATP synthesis can be done a bazillion
> different ways- are you asking why ATP?

A "bazillion" different ways there may be, but this just isn't enough.
The ratio of ways that will work compared to those that won't is
extremely tiny. It can only be done with the use of a relatively
limited number of very specific arrangements of a rather large number
of protein parts associated with the cellular membrane in very specific
ways. This translates into a very tiny portion of sequence space that
could actually give rise to an ATP producing system that is actually
beneficial by the time it happens to come on the scene.

Remember now, you have to take into account the notion that the
production of ATP alone isn't beneficial unless there is a system
already there that can use ATP to some benefit. This sort of required
integration makes the beneficial evolution of such a system much more
complicated.

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 26, 2006, 5:14:37 AM8/26/06

Perplexed in Peoria wrote:

> > You seem to me, at this point, to be confusing ratio with starting
> > point. The ratio is still what it is. It seems to me that you are
> > simply suggesting that the starting points are much closer to the
> > targets than I seem to realize. Correct? Not nearly as many random
> > steps need to be taken as I seem to be suggesting - right?
>
> Yep. You got it exactly.
>
> > Of course, I've argued that gene duplication does not make novel
> > starting points. It only makes more of the same starting point. You
> > are still left with having to cross a gap that includes all potential
> > sequences - even the ones that won't fold to make much of anything.
> > This might be taken to mean that the random walk/sampling required is
> > not significantly reduced.
>
> But there aren't gaps - whole impassable channels - composed of
> sequences that won't fold. Sewell Wright has confused generations
> with his metaphor of a 'fitness landscape'. Read the recent book
> by Sergei Gavrilets and reset your intuitions on this point.
>
> What you seem to be suggesting is that gene duplication does nothing
> more than add more paper. The writing on that paper is totally
> useless in terms of producing another page for 'the book' by mutation
> and natural selection. The paper might as well have been blank to
> begin with. Just not so. The page contains whole words which merely
> need to be rearranged to form whole new sentences.

Yes, but this rearrangement is what creates the gaps. This
rearrangement isn't easy. It takes The words simply aren't lined up
correctly and require a great deal of shuffling to end up on a new
beneficial arrangement. The number of changes that need to be realized
to get from one steppingstone to the next in the pathway of a function
like the flagellar motility system are many dozens if not hundreds of
changes. A gap of just a few dozen changes would be uncrossable this
side of trillions of years of time - on average.

That's the whole problem.

> > Unless, unless of course the genome already has the needed part to make
> > the next step in the genome pre-formed. Your argument seems to suggest
> > that the odds that this will in fact be the case are pretty good! -
> > since many of the non-workable potential sequences are screened out
> > ahead of time by default. And, this is in fact true at lower levels of
> > functional complexity. However, at higher and higher levels, the size
> > of the step to the next novel function grows linearly. It becomes
> > harder and harder to find a pre-existing sequence that would cross this
> > step in one fell swoop with one single mutation event - such as a
> > duplication and insertion of just the right sequence into the correct
> > spot. The problem is that the odds that the needed sequence that would
> > fill the gap actually exists preformed in the same genome decrease
> > exponentially as well with each step up the ladder.
>
> I think that Dawkins's "weasel' game has misled you into how evolution
> actually works. Either that, or you have been misled by that "in His
> image and likeness" thing. There is no predetermined end point to
> be reached. Instead there is a lot of stumbling around as proteins
> first take one role all the time (doing X, say), then gradually are
> modified to do X only if Y is present in the environment (call it Y -> X)
> and then further mutate into something like (X -> ~Y). It is not
> a straight line path from something that doesn't work properly to
> something that does.

I never said it was. The problem is that there isn't any path at all
from X to Y at higher levels. X is completely surrounded on all sides
by non-beneficial sequence options. The only way for X to get to Y or
to any other potentially beneficial island cluster of beneficial
sequences is to randomly swim through or jump through the ocean of
non-beneficial sequences. Y will not start working at all, not even a
little bit, until the sequence meets the minimum requirements of size
and specific arrangements that Y requires. There is no gradual
modification and increase in the function that Y would produce until
this minimum threshold is realized.

That's the difference between the evolution of a functional system like
flagellar motility and Dawkins' "weasel" program - where each character
change was compared to a template and those offspring with the most
matches to the template where selected for increased reproductive
rates. That sort of thing simply can't be done to evolve a function
like flagellar motility because there is not such template to match
individual character changes against.

> > If you want to use a specific example, please do explain a specific
> > functionally beneficial step in the evolution of the flagellar system
> > from some proto form.
>
> I'm pretty sure that one has already been sketched - for example,
> at the t.o. website.

Where? List the link . . . I do discuss a paper by Matzke that is
linked on the T.O. website on my own website at:

http://www.detectingdesign.com/flagellum.html

> > Or, provide any actual experimental
> > demonstration of the evolution of any new function that require more
> > than a few thousand fairly specified bp of DNA.
>
> Hmmm. Let's see. That would require that I bio-engineer something
> like (say) 4000 different strains of bacteria - each containing
> proto-flagelar proteins doing something useful, with the first not
> having anything like a flagellum and the last with a fully functional
> flagellum. And when I line up these 4000 petri dishes in a row,
> each differs from its predecessor by only a single mutation. Is
> that what you are asking for?

Just show me were any new function has been observed to evolve - a
function that requires at a few thousand fairly specified bp of DNA to
code for it. You don't have to do the work yourself. Just show me a
published paper describing such an observation.

< snip >

> > Forget about abiogenesis. I'm only interested in evolutionary
> > potential given the starting point of a living creature that can
> > reproduce itself. I really don't think you've solved the problem. All
> > your theory does is create little islands that happen to link up with
> > each other like a sticky bubble gum. This does make evolution quite a
> > bit easier at very low levels - where pre-formed chucks of this can
> > combine with pre-formed chunks of that to make a novel functional
> > system. However, at higher and higher levels of minimum size and
> > specificity requirements, the odds that the right pre-formed chuck will
> > actually exist anywhere in the genome to get you to the next step in
> > the pathway toward any higher level system drop off exponentially - and
> > you are back to where you were to start with.
>
> And I think that you are trying to scale "methinks it is a weasel" up
> to a monkey typing "Hamlet". Evolution just doesn't work that way.

Actually, evolution is supposed to work exactly that way - random
mutations and function-based selection. At higher and higher levels of
functional complexity, you have to rely more and more on your typing
monkeys to find those rarer and rarer potentially beneficial sequences.
The monkeys can type or copy and paste or any other sort of random
rearrangement of what already works and it still will take trillions
upon trillions of years to find anything beyond very low levels of
functional complexity.

> > > We can talk about abiogenesis some other day. You

> > > can even talk some more about cilia and flagella.
> > > I certainly haven't completely explained them here.
> > > All I have done is to show that simple multiplication
> > > of probabilities is not the way to approach these
> > > kinds of evolved 'IC'.
> >
> > I really don't think you've done what you think you've done at all.
> > The islands of potentially beneficial sequences simply become more and
> > more stretched out at higher and higher levels of functional complexity
> > until the bridges between them simply snap apart and they become truly
> > isolated in a very remote way. Now, no single multicharacter
> > insertion/deletion/translocation etc is going to get you there.
> > Multiple mutations involving multiple characters each are required.
> > And, multiplication of the odds is back . . . and at very low levels.
>
> It must be very frustrating for you when knowlegeable people don't
> share your intuitions. Hell, I know it is. It is frustrating to
> me in the abiogenesis field where everyone else seems to be stuck
> on "First you create the building blocks, then you join the blocks
> together".

Arguments from authority aren't really helpful now are they? If you
think you understand the problem then present a real argument. The fact
that I am in the minority and you in the majority really doesn't have
much explanatory value. You can say that you or someone on your side
knows the answers, but that isn't the same thing as actually providing
the answers now is it?

Sean Pitman
www.DetectingDesign.com

Seanpit

unread,

Aug 26, 2006, 5:23:27 AM8/26/06

Ron O wrote:

> > Do antibodies undergo random changes that are preferentially
> > selectable, based on functional differences, over generations of immune
> > cells? How is this not a type of evolution? A new function is realized
> > over time via random mutation and function-based selection - right?
> > Are you really arguing that because this function isn't passed on to
> > the next human generation via coding changes in the gametes means that
> > it isn't a type of evolution at all? Really?
>
> Antibodies that undergo random changes that are selected for based on
> functional differences only demonstrates that your bogus notions of
> probability are nonsense. It is an example of protein evolution in
> real time that anyone can study. It demonstrates that even new enzyme
> activities can develop in less than 10E12 events. It demonstrates that
> your estimates are bogus and that proteins are more plastic than you
> think and that it isn't difficult to evolve new functions from existing
> protein sequences.

Of course antibodies evolve greater specificity for specific antigens
very quickly over just a few generations. This is very easy to explain
because it is based on improved binding of a protein that already
binds, in an beneficial way, to a particular protein antigen sequence.
Every single character change that results in an improvement in
antibody binding to the antigen will be rewarded with improved
reproductive advantages. In this way, the antigen acts as a template
for antibody matching - just like in Dawkins' famous "weasel"
algorithm.

The odds that a particular antibody mutation will result in an improved
binding to the antigen are quite high. That is why antibody evolution
happens so rapidly. The problem is that not all functions can evolve
this way - with the use of a template. For example, the flagellar
motility system cannot evolve one residue change at a time via template
matching. There simply is no series of beneficial steps that are
separated by only one or two residue differences in the pathway of
flagellar evolution.

And, therein lies the gap problem.

> What an idiot, or is it simple dishonesty this time?

Well, I can assure you that I'm being quite honest in these threads.
So, I guess I'm left with the "idiot" option? ; )

> Ron Okimoto

Sean Pitman
www.DetectingDesign.com

Ron O

unread,

Aug 26, 2006, 8:31:15 AM8/26/06

So what? What is the difference to what you claim can't happen? Put
your finger on it and demonstrate that there is some very important
difference. Don't just assert that there is a difference, but
demonstrate it. If you claim that there is a gap of 10 or 20
demonstrate it.

Not only that, but the antibodies have specificity to the antigens by
chance. You can make up a synthetic antigen that has never been seen
in nature and you will form specific antibodies to it. Not just one,
but many different ones using many different sequences because you can
generate these antibodies in a wide range of different species. So
where did this initial specificity come from? How is it different from
taking an existing ATPase and using it to make something like the
flagellar motor? You make these assertions, but you can't back them
up. Why do you think that the assertions are worth anything?

>
> The odds that a particular antibody mutation will result in an improved
> binding to the antigen are quite high. That is why antibody evolution
> happens so rapidly. The problem is that not all functions can evolve
> this way - with the use of a template. For example, the flagellar
> motility system cannot evolve one residue change at a time via template
> matching. There simply is no series of beneficial steps that are
> separated by only one or two residue differences in the pathway of
> flagellar evolution.

How high are they and why are they different from any other protein
function? Since you can't demonstrate that any other protein sequence
isn't just as plastic and variable when it comes to doing things, what
is your beef?

>
> And, therein lies the gap problem.

Demonstrate that there are gaps. Point them out and show us how big
they are. Since you have never been able to do this for even a gap of
three mutations, what is your argument worth?

What is really sad is that you are using the ID scam of the flagellum
when you know that you can't trust the ID/creationist scam artists
anymore than you can trust the junk on your web page. If any of this
stuff was worth anything you wouldn't be dinking around using bogus
arguments from people that you know have lied to you for years. They
had their chance in Ohio and Dover to demonstrate that they had an
argument about the flagellum, but what did they come up with? Behe's
excuse for putting forward such a bogus argument was that he could test
it like in science fiction even though he couldn't test it in reality.
How bogus is that? Fictional testing is just what you do when you make
these bogus assertions and you never back them up. The flagellar
argument never amounted to anything. You know this for a fact because
the ID scam artist that lied to you about it quietly dropped the ID
scam for a replacement scam that doesn't even mention that ID ever
existed. You kept believing the junk even after Ohio when they were
not able to come up with a scientific theory of ID to teach, and you
even tried to defend ID after Dover. What is wrong with you? When the
scam artist that fooled you have moved on to another scam, what the
heck do you think that you are doing beating a dead horse?

This is just sad and at some level you know it. If creationist like
yourself had valid arguments we would all know about it by now. Get a
clue and get some help. I can't believe that there isn't someone that
you trust that can set you straight about this. It is black and white
that you have been scammed. If it wasn't Dover and Ohio would have
totally different outcomes.

>
> > What an idiot, or is it simple dishonesty this time?
>
> Well, I can assure you that I'm being quite honest in these threads.
> So, I guess I'm left with the "idiot" option? ; )

Basically, you are worse off then an idiot. The insanity defense is
about all you have left. You are too far gone for it to be simple
incompetence at this point, and at some level you probably know it. Do
you want me to quote your defense of ID when you claimed that you could
do better than the rubes that ended up taking the replacement scams
from the guys that you still think have valid arguments? Do you still
think that you could do better than the ID scam artists did in Ohio and
Dover? If you do, why don't you consider that to be insanity? Just
think if it was someone else. Get someone you trust to clue you in,
and if you want to claim honesty and integrity, put up front on your
web page that even you don't trust the junk in it. If you trusted it
you would be able to demonstrate that it means what you think, and if
you could do that we wouldn't have any arguments.

Ron Okimoto

Seanpit

unread,

Aug 26, 2006, 11:35:21 AM8/26/06

Ron O wrote:

> > Of course antibodies evolve greater specificity for specific antigens
> > very quickly over just a few generations. This is very easy to explain
> > because it is based on improved binding of a protein that already
> > binds, in an beneficial way, to a particular protein antigen sequence.
> > Every single character change that results in an improvement in
> > antibody binding to the antigen will be rewarded with improved
> > reproductive advantages. In this way, the antigen acts as a template
> > for antibody matching - just like in Dawkins' famous "weasel"
> > algorithm.
>
> So what? What is the difference to what you claim can't happen? Put
> your finger on it and demonstrate that there is some very important
> difference. Don't just assert that there is a difference, but
> demonstrate it. If you claim that there is a gap of 10 or 20
> demonstrate it.

I have, many times. I've shown that the gaps involved between
potential steppingstones along the pathway of higher level functions
are many dozens of residue changes wide:

http://www.detectingdesign.com/flagellum.html

> Not only that, but the antibodies have specificity to the antigens by
> chance.

Right . . . but the range that need to be covered in order to have at
least some specificity for all foreign antigen types is limited so that
the immune system needs to produce no more than 20 or so billion
different types of antibody sequences up front. After this initial
casting of the net, at least some of these antibodies will bind to at
least some selectably beneficial degree to any foreign antigen. The
evolution of additional specificity, following this initial exposure,
will happen rapidly.

> You can make up a synthetic antigen that has never been seen
> in nature and you will form specific antibodies to it. Not just one,
> but many different ones using many different sequences because you can
> generate these antibodies in a wide range of different species. So
> where did this initial specificity come from?

The initial range of antibody sequences was programmed by design to
produce this range and function of the antibodies and the overall
immune system. The overall immune system function is highly complex and
did not evolve. It was designed. They only aspect of the immune system
that does evolve is antibody specificity for the antigen.

> How is it different from
> taking an existing ATPase and using it to make something like the
> flagellar motor?

Because, the function of the flagellar motor is not there originally
like it is for the antibody binding. There is no ATPase that has even
a little bit of the flagellar motility function to start out with.
There is no template upon which to build up the flagellar motility
system one tiny mutation at a time. All these are significant
differences that produce the gap problem for evolution.

> You make these assertions, but you can't back them
> up. Why do you think that the assertions are worth anything?

I've shown you example after example. The evidence in literature is
overwhelming. Evolution of functions that cannot use a template just
doesn't happen beyond very low levels of functional complexity - i.e.,
those functions that require a minimum of more than a few thousand
fairly specified bp of DNA. There's not a single example of such a
thing happening in real life nor is this notion statistically tenable
on paper.

> > The odds that a particular antibody mutation will result in an improved
> > binding to the antigen are quite high. That is why antibody evolution
> > happens so rapidly. The problem is that not all functions can evolve
> > this way - with the use of a template. For example, the flagellar
> > motility system cannot evolve one residue change at a time via template
> > matching. There simply is no series of beneficial steps that are
> > separated by only one or two residue differences in the pathway of
> > flagellar evolution.
>
> How high are they and why are they different from any other protein
> function?

The odds that a mutation will result in improved antibody-antigen
binding, when the initial binding isn't the most ideal, are extremely
good - perhaps as high as 1 in 2 or 3 mutations to begin with.

The reason for this is the same reason why Dawkins' "weasel" program
works so well. Every single character in a random sequence that gets
mutated to match the template is selected for improved reproductive
fitness. In this particular example, the odds that a mutation will
change a character that isn't "right" to the correct type of character
for that position is no less than 1 in 27. Those are extremely good
odds and result in very rapid evolution of a random sequence to "match"
the template sequence.

Now, when it comes to the flagellar system, there is no template with
which to compare every single residue difference and select every
single residue change as an improvement or a detriment. Without this
template, the finding of the next beneficial steppingstone starts to
involve more and more non-beneficial changes. And, this gap of
non-beneficial changes grows linearly with each increase in the minimum
size and specificity requirement of the functional system. A linear
increase in these minimum requirements translates into an exponential
increase in the random walk/random selection time needed before success
can be realized - on average.

> Since you can't demonstrate that any other protein sequence
> isn't just as plastic and variable when it comes to doing things, what
> is your beef?

Oh, but I can. Do you realize that every single antigen will have at
least some match to an antibody of a well-working immune system?
Consider then your notion that all other systems of function will be
just as easily found by looking at a really simple one that is not
based on template matching - like the lactase function. Many types of
bacteria simply cannot evolve the relatively simple lactase function
despite high mutation rates and a high selective advantage if the
lactase function were ever realized. Some bacteria have been observed
to be lactase negative for over 40,000 generations of time in specific
experimental conditions. Others have been lactase negative for over 1
million generations according to hospital logs.

Scientists like Barry Hall have referred to these bacteria as having
"limited evolutionary potential". Now Ron, what is it, exactly, that
limited the evolutionary potential of these bacteria? What made them
incapable of evolving the lactase function despite the significant
advantage that they would have gained if they were able to do so?

The fact is that if anything in the bacterial genome of these limited
bacteria were just one or two residue changes away from the lactase
function, the lactase function would have evolved - and quickly. We
know this because such an experiment has been done and was successful.
So, the fact that many types of bacteria cannot evolve the lactase
function can only mean one thing. There is a larger gap between what
they have and the minimum requirements of the relatively simple single
protein lactase function.

In other words, this is proof of a gap problem starting out at a
relatively low level of functional complexity. There are just no two
ways about it.

> > And, therein lies the gap problem.
>
> Demonstrate that there are gaps. Point them out and show us how big
> they are. Since you have never been able to do this for even a gap of
> three mutations, what is your argument worth?
>
> What is really sad is that you are using the ID scam of the flagellum
> when you know that you can't trust the ID/creationist scam artists
> anymore than you can trust the junk on your web page. If any of this
> stuff was worth anything you wouldn't be dinking around using bogus
> arguments from people that you know have lied to you for years. They
> had their chance in Ohio and Dover to demonstrate that they had an
> argument about the flagellum, but what did they come up with? Behe's
> excuse for putting forward such a bogus argument was that he could test
> it like in science fiction even though he couldn't test it in reality.
> How bogus is that? Fictional testing is just what you do when you make
> these bogus assertions and you never back them up. The flagellar
> argument never amounted to anything. You know this for a fact because
> the ID scam artist that lied to you about it quietly dropped the ID
> scam for a replacement scam that doesn't even mention that ID ever
> existed. You kept believing the junk even after Ohio when they were
> not able to come up with a scientific theory of ID to teach, and you
> even tried to defend ID after Dover. What is wrong with you? When the
> scam artist that fooled you have moved on to another scam, what the
> heck do you think that you are doing beating a dead horse?

These are my own arguments Ron. They are not based on the arguments of
others - not when it comes to genetics at least. I came up with these
ideas all by myself after doing my own research into the problem. I
really don't care if I'm the only one left to say so. The ToE just
doesn't make rational sense. It is statistically untenable and I'm
truly amazed that you and many other otherwise intelligent people have
been so taken in by it.

> This is just sad and at some level you know it. If creationist like
> yourself had valid arguments we would all know about it by now. Get a
> clue and get some help. I can't believe that there isn't someone that
> you trust that can set you straight about this. It is black and white
> that you have been scammed. If it wasn't Dover and Ohio would have
> totally different outcomes.

Not true. The ToE isn't just a cold rational "scientific" notion. It
is believed with a strong passionate faith by the mainstream scientific
community. It has taken on religious devotion. Such devolution is not
easily overcome - even by the strongest rational scientific evidence to
the contrary.

> > > What an idiot, or is it simple dishonesty this time?
> >
> > Well, I can assure you that I'm being quite honest in these threads.
> > So, I guess I'm left with the "idiot" option? ; )
>
> Basically, you are worse off then an idiot. The insanity defense is
> about all you have left.

LOL - bummer ; )

>You are too far gone for it to be simple
> incompetence at this point, and at some level you probably know it. Do
> you want me to quote your defense of ID when you claimed that you could
> do better than the rubes that ended up taking the replacement scams
> from the guys that you still think have valid arguments? Do you still
> think that you could do better than the ID scam artists did in Ohio and
> Dover?

Actually I don't think the outcome would have been any different if I
had presented my ideas in Ohio or Dover. I think this whole thing is
far beyond rational presentation of ideas. It is about one religion
vs. another. And yes, the ToE is held with just as much passion,
fervor and faith by you guys as any religious belief.

> If you do, why don't you consider that to be insanity? Just
> think if it was someone else. Get someone you trust to clue you in,
> and if you want to claim honesty and integrity, put up front on your
> web page that even you don't trust the junk in it. If you trusted it
> you would be able to demonstrate that it means what you think, and if
> you could do that we wouldn't have any arguments.

There is a big difference between presenting very good evidence and
getting someone else who is strongly biased against it to accept it for
what it really is. You can only lead a horse to water you know . . .

And, remember Ron, many very good ideas were scoffed to scorn
originally by the mainstream scientists of the day. Be careful when
you call someone an idiot or insane. Sometimes, these "crazy" people
are actually right after all.

Seanpit

unread,

Aug 26, 2006, 11:42:38 AM8/26/06

The fact that any other 3D arrangement could have been coded for Von.
That is what makes it so rare in the vast space of potential 3D
arrangments of the residues.

> What peculiar constraints on
> genetic sequence does such a requirement impose, Sean? Where are they?

The constraints need to produce one particular 3D sequence when any
other of a vast host of options could have been produced. Again Von,
the underlying code cannot be less constrained than the requirements of
the final product.

If you think otherwise, please do explain your own basis for such a
notion. Explain to me how the underlying code could be less constrained
than the final product. Of course, I keep asking for this explaination
but you specifically say that you don't need to provide this
explanation. You don't feel the burden to defend your own position,
yet you keep demanding some sort of explanation from me that simply
doesn't make any sense in light of the obvious truth of that an
underlying code cannot be less complex than the requirments of the
final product.

Von R. Smith

unread,

Aug 26, 2006, 11:51:50 AM8/26/06

Seanpit wrote:
> Von R. Smith wrote:
>
> < snip >
>
> > > > On the other hand, when trying to play up the complexity of the
> > > > flagellum, he will point out that one needs all of the 20-odd
> > > > structural proteins, plus the supporting cast of chaperones, transport
> > > > proteins, etc., for it to work.
> > >
> > > That's not all. Not only does a flagellar system need all of its
> > > parts, it needs all of its parts to be specifically arranged with each
> > > other in three dimensions.
> >
> > ...and I am still waiting for you to describe the constraints on
> > *sequence* variability that this imposes.
>
> How is it wrong to suggest that the underlying code has to be just as
> specified as the specificity limitations of the final product?

Oh, so you're just *suggesting* it? Can you point to any actual
additional constraints on genetic sequence imposed by a "3D
requirement" or not?

>
> > > > Sean won't address (or even
> > > > acknowledge unless pointed out) the fact that sub-components of the
> > > > flagellum have recognizable independent uses, or that most of the
> > > > individual proteins have identifiable non-flagellar homologs, or that
> > > > one can propose plausible independent functions for the ancestors of
> > > > those proteins.
> > >
> > > This is a deliberate lie. I have addressed this point extensively both
> > > in this forum and on my website.
> >
> > As with the word "explain", you and I apparently have rather different
> > notions of what it means to "address" an issue.
>
> You know that I do recognize the fact that sub-components of the
> flagellar motility system do in fact carry independent useful
> functions. You yourself realize that I've recognized this for a long
> time now. Therefore, how is it anything but a deliberate
> misrepresentation on your part to say otherwise?

Notice the phrase "unless pointed out". Somebody else had already
noticed that your argument as stated earlier in this thread failed to
factor in the potential for independent utility of the sub-components,
and they have continued to do so as the thread has progressed. The
extent of your *argument* against this has been to say: "Yeah, but I
don't buy it; there has to be neutral gaps somewhere". Then you go
right back to refuting your strawman. That does not qualify as
addressing the issue, in my view, so I stand by what I wrote above.

We have had this discussion before, so let's not pretend that you
misunderstand my point. A strawman is first and foremost a failure of
logical relevance. The point is not so much that you put words in your
opponent's mouth; the point is that your *argument* attacks an
irrelevant scenario, but you nonetheless seek to persuade your audience
that it has traction against your opponent's actual position.
Otherwise, why would you spend so much bandwidth on it?

Saying that you disagree with your opponent's position does not entitle
you to ignore it while pretending to refute it, and that is exactly
what you do; your rhetorical setup is basically: "I don't buy your
position, so I'm going to ignore it and refute this other model
instead, and then pretend that it poses a problem for you." If you
don't like calling that a strawman, you can call it a non sequitur or
red herring instead. Pick your favorite fallacy of relevance; it will
not rehabilitate the logical problem with your argument.

>
> > If the steps were individually selectable, then the involvement of a
> > dozen or more proteins would not be a real problem for evolution.
>
> That's quite true, as I've pointed out myself many many times. The
> problem is that the individual steps start becoming bigger and bigger
> at higher and higher levels. The size of the step that used to result
> in a new beneficial function at lower levels no longer does the trick.
> Now, instead of crossing a gap of just one or two residue differences,
> a gap of dozens of residues differences must be overcome.

Ah, you see, but the burden is on you to demonstrate that there is any
such *problem, and yet you never have done so; you have merely asserted
it. And you then attribute this problem, without justification, to
your opponent's position, and then concentrate on refuting the alleged
problem. So if you don't like having your argument called a strawman,
get to work on *demonstrating* the existence of these neutral gaps, and
showing that they separate existing systems from any possible
functional homologs, making them unevolvable. Until then, claiming
that these neutral gaps are a problem entailed by your opponent's
position remains a strawman.

>
> > But
> > here as in so many other posts you fail to note that distinction;
> > rather, you argue from the unstated assumption that a function
> > involving interactions among many different proteins must hit upon all
> > those interactions at once.
>
> I've never said this. In fact, I've specifically stated the opposite
> many many times - directly to you. The fact that you continue to
> present this notion as representative of my position is no less than a
> deliberate misrepresentation on your part.

I stand by what I said, and by the reasons I have given for it. I know
that you do not like it. I know that you have a strong interest in
denying it. Perhaps, given your obvious limitations in math, you
honestly do not see the problem. If the proteins do not have to hit on
all the interactions at once, then the statistics do *not* "really
start adding up". Your line of argument here only has traction in the
case that they must do so. You can verbalize your opponent's position
accurately all day long; it won't make the *arguments* you present any
less directed against a strawman. And once more, if calling it a
"strawman" is the only thing standing between you and seeing what the
problem is, then you can substitute some other fallacy of relevance, if
you like.

>
> For example, the evolutionary pathway of a flagellar motility system
> need not evolve all the parts of the flagellar motility system all at
> once. Certainly not. There are definitely steppingstone functions
> along the pathway that would yield benefits before reaching the final
> flagellar motility system. However, these stepping stones are,
> individually, too far apart to reach any one of them from any other.
> That's the problem. It isn't that just the flagellar motility system
> cannot be evolved. It is that none of the steppingstones in the pathway
> can be evolved. That's the problem.

No, that's your assertion. It only becomes a problem once you have
*demonstrated* it to be one. But you never do that; all you do is
pretend that your opponent's argument actually entails such a problem,
and that all you need by way of refutation is to demonstrate just how
much of a problem this alleged problem is.

>
> > Likewise, this strawman seems to be the
> > unacknowledged basis for your whole "four 6s in a row" vs. "two pairs
> > of two 6s" analogy; again, you are trying to suggest that the proteins
> > in a function with a "3D requirement" must come into existence all at
> > once, rather than appear gradually. If you disagree, then tell me what
> > else your "four 6s in a row" actually refers to.
>
> The four 6s in a row represents the demands of the system in question.
> It represents the rarity of a specific sequence requirement in sequence
> space. This does not mean, however, that a function that requires just
> two or even three 6s in a row couldn't be useful in a given "genome".
> Of course, this would mean that a bunch of double and triple 6s would
> be all over the place. And, of course, this would mean that it would
> be quite a bit easier to realize the four 6s in a row. However, the
> function that requires that four sixes be in a row still requires that
> four 6s be in a row. That function is still quite rare in sequence
> space - exponentially rarer than the function that requires two double
> sixes.
>
> Do you understand the difference here now?

No, because in the above statement, you never told me what the "four 6s
in a row" actually refers to. "The demands of the system in question"
is vapor. If you can't answer the question, just say so.

> The minimum part
> requirement for a function doesn't mean that there are no intermediate
> steps that are also functionally beneficial. It just means that its
> own function requires a specific type of sequence and that specificity
> and minimum size translates into rarity within sequence space.

Then why, if evolution does not have to proceed by your strawman, would
4 6s in a row be exponentially harder to realize than two double 6s as
you have repeatedly claimed? With a suitably selectable pathway, there
would be no difference in evolvability between 4 6s in a row and a pair
of 6s followed by another pair of 6s. There is only a major,
exponential difference under your strawman model of evolving all four
6s in a row at once.

>
> < snip >
>
> > > You may say that my views are wrong here, but you really can't say that
> > > I'm building a strawman to misrepresent your true position - unless you
> > > don't understand the definition of a strawman argument (aka Howard
> > > Hershey)
> >
> > I do not think you are in any position to fault other people's grasp or
> > use of terms. The accusation of a strawman rests upon your repeated
> > use of it as your model for what the evolution of complex structures
> > and functions entails. Once it is pointed out that you are *not*
> > entitled to assume that evolution of complex functions must proceed by
> > your strawman version of it, all that is left of your argument is bare
> > incredulity and rejection.
>
> You can argue that my model isn't correct, but you cannot argue that
> I'm using a strawman argument to misrepresent your position Von. A
> strawman argument is a misrepresentation of another's position in order
> to attack a weaker non-real version of an opponent's views.

As I understand and use the term, a strawman is a *logical* fallacy
that consists of presenting a refutation of a weaker, irrelevant
argument as if it were a refutation of your opponent's real one.
Outright misrepresentation of what your opponent has said is not a
requirement. Once again, if you want to quibble and call it a red
herring or non sequitur instead because you don't like having it called
a "strawman", fine. It won't save the relevance of your argument.

> I've not
> done this. I've not misrepresented your own position - your actual
> views. I've presented your views correctly. I've just presented my
> own views, as my own, not calling them your views. You may disagree
> with my views on how evolution would have to work, but they are by no
> means labeled by me as your views. They aren't your views. They are my
> views. By definition then I'm not building a strawman
> misrepresentation of your views.
>
> Look up the definition of a strawman Von. You really are misusing the
> term.

I can find definitions of a strawman fallacy that refer to actively
misrepresenting an opponent's position, and others that do not. I am
using one that does not. Here is an example:

"The Straw Man is a type of Red Herring because the arguer is
attempting to refute his opponent's position, and in the context is
required to do so, but instead attacks a position-the "straw
man"-not held by his opponent. In a Straw Man argument, the arguer
argues to a conclusion that denies the "straw man" he has set up, but
misses the target. There may be nothing wrong with the argument
presented by the arguer when it is taken out of context, that is, it
may be a perfectly good argument against the straw man. It is only
because the burden of proof is on the arguer to argue against the
opponent's position that a Straw Man fallacy is committed. So, the
fallacy is not simply the argument, but the entire situation of the
argument occurring in such a context."

http://www.fallacyfiles.org/strawman.html

>From a logical point of view, not actively attributing your strawman to
your opponent actually makes your argument *worse*, not better.
Misrepresenting your opponent's actual position would at least give you
a pretext, albeit a bogus one, for attacking the strawman as if it had
any traction against your opponent's argument. But since you are
obviously more concerned about looking bad than you are about being
illogical, you would rather protest your innocence than fix your
argument. Once more: if it really sticks in your craw to call it a
strawman, you can call it a red herring instead. Pick your favorite
fallacy of relevance; it won't help your case.

I didn't say it wasn't. I said that it was one of Matzke's proposed
steps, and it is. You keep saying that you don't require a real time
demonstration of a flagellum appearing from scratch; any step in the
pathway will do. But as soon as you are confronted with such a step,
you shift the goalposts out to something very like the very strawman
you keep disowning: OK, so instead of insisting on the entire
flagellum from scratch all at once, you just want one of the major
sub-assemblies from scratch all at once. Sounds like the same strawman
to me.

>
> > Howard Hershey also gives examples of re-evolving the
> > protein-protein interactions between fliF and fliG. I pointed these
> > out to you on at least two other occasions, and you have never
> > commented, at least not in response to me.
>
> And this is like messing a pre-existing system up by throwing one tiny
> mutation into the works and then reversing the damage done with one
> tiny reverse mutation. Give me a break! I'm just amazed by the stuff
> you and Howard come up with in order to try to avoid the main issue.
> Do you know that cavefish that do not grow eyes anymore have a single
> point mutation that causes this lack of eye growth? If placed back in
> a lighted environment, their offspring quickly evolve their eyes back
> again because this single point mutation is relatively easy to reverse.
>
>
> Demonstrating that it is easy to move one tiny step off an island of
> beneficial function, and then back on the island with one tiny reverse
> step, is not the same thing as demonstrating that it was easy to find
> the island starting from any other island to begin with.

I see. So I can't present slight, gradual changes on a possible
evolutionary pathway for a flagellum as examples of slight, gradual
changes on a possible evolutionary pathway for a flagellum. The only
example you would accept is the evolution of the flagellum from scratch
in real time. Or maybe just evolution of an entire TTSS from scratch
in real time. But you aren't insisting on some strawman version of
evolution. No, Sir.

>
> > > You're just making this stuff up as you go along - hoping that mere
> > > bluster will be good enough to prop up your baseless position . . .
> >
> > Project much?
>
> Where is your evidence Von? That's all I'm asking for. What have you
> actually brought to the table? What do the "evidences" you've just
> listed here really amount to but so much hot air?

I have presented it, and as I predicted, you promptly made excuses and
then shifted the goalposts right back out to your
"[major-sub-assembly-of]flagellum-all-at-once-from-scratch" strawman.
The one you keep saying you aren't using.

Oh, and speaking of evidence vs. hot air, when are you going to get
around to telling me what additional constraints a "3D requirement"
imposes on a genetic sequence coding for it?

Von R. Smith

unread,

Aug 26, 2006, 11:56:49 AM8/26/06

So, in other words, you can't answer the question.

>
> > What peculiar constraints on
> > genetic sequence does such a requirement impose, Sean? Where are they?
>
> The constraints need to produce one particular 3D sequence when any
> other of a vast host of options could have been produced. Again Von,
> the underlying code cannot be less constrained than the requirements of
> the final product.
>
> If you think otherwise, please do explain your own basis for such a
> notion. Explain to me how the underlying code could be less constrained
> than the final product. Of course, I keep asking for this explaination
> but you specifically say that you don't need to provide this
> explanation. You don't feel the burden to defend your own position,
> yet you keep demanding some sort of explanation from me that simply
> doesn't make any sense in light of the obvious truth of that an
> underlying code cannot be less complex than the requirments of the
> final product.

If you say that sequences coding for a function with a "3D requirement"
have some additional degree of constraint, then the burden is on you to
describe what those constraints are. In spite of repeated attempts to
get you to explain what they are, you still have not done so.

What parameters are more constrained, Sean?

Seanpit

unread,

Aug 26, 2006, 12:13:12 PM8/26/06

Robert Maas, see http://tinyurl.com/uh3t wrote:
> > From: "Seanpit" <seanpitnos...@naturalselection.0catch.com>
> > The problem is, the driving forces of evolution, i.e., random
> > mutation and natural selection, just can't create systems of function

> > that require a minimum of more than a few thousand fairly specified

> > bases of DNA.
>
> Why couldn't such a multi-thousand-base sequence for this "new"
> function have evolved from some other sequence of comparable length
> that coded some "old" function, requiring only five or ten changes from
> the old sequence to the new sequence?

This could happen, but the odds that the "old" function of equivalent
length will only be 5 or 10 residue differences from the "new" aren't
very good. I mean, you could win the lottery 5 times in a row - right?
But what are the odds. The same thing is true of the odds that
anything in the genome will be right next door to a new high-level
system of beneficial function. And, by the way, a gap of 10 specific
residues differences needed in a specific location is rather huge -
requiring billions and even trillions of years to cross for an average
sized population.

> > Of course an entirely new system doesn't need to evolve to detect
> > such antigen changes! If you are talking about the evolution of the
> > immune system, then no, I don't believe that the immune system evolved
> > from ancestor creatures that didn't have an immune system.
>
> You seem to be claiming that the immune system itself was a *new*
> system unrelated to anything that existed before. On what basis do you
> make such a claim?

The fact that the immune system as a whole is far too complex to have
evolved from anything that is remotely likely to have existed before.
This is not to say that there are no sequence similarities with other
proteins in other systems of function. However, these are based on
common design, not common evolutionary ancestry. The basis for this
argument is both statistical and demonstrable in real life. There
simply are no examples of any new function evolving that requires more
than a few thousand fairly specified bp of DNA at minimum.

> > The minimum coding requirement for a useful immune system is far too
> > complex for evolutionary mechanisms to achieve even in trillions upon
> > trillions of years of time.
>
> Let's do some arithmetic. Suppose about once every million years
> there's a burst of adaption, whereby ten DNA bases are changed,
> resulting in a new function different from before.

The odds that 10 bp changes would hit upon a new beneficial high-level
function are extremely remote.

> So over the course
> of a billion years, one thousand of these bursts would accumulate,
> totalling ten thousand DNA-base changes, i.e. virtually every DNA base
> (in the multi-thousand sequence which now codes for the immune system)
> would be different now from a billion years ago. That doesn't match
> your claim that trillions of years would be required.

It also doesn't match statistical likelihood. Natural selection has
the ability to maintain what is already in good working order. It
doesn't have the ability to help random mutations find novel beneficial
sequences before they are actually found by random mutations. The odds
that ten random mutations will happen upon a new high-level function
just aren't nearly as good as you seem to imagine. You don't seem to
understand the relative rarity of higher-level systems in sequence
space. It's like hitting upon a particular atom in the entire universe
after taking only 10 random steps. What are the odds of that? That is
what you really need to ask yourself here.

> > Duplicate genes or duplicate regions of a genome may indeed be many
> > thousands or tens of thousands or even millions of bases in size. Yet,
> > no new function is realized via a simple duplication of what was
> > already there. The only thing duplication does is make two out of one.
>
> Correct so-far. But then one of the copies begins mutating toward new
> functions, no longer required to do the old function because the other
> copy can do it just fine.
>
> > We are talking about new functions here Marc - not more of the same
> > thing.
>
> There's no such thing as *new* functions. Every function is a small
> change (in DNA sequence) from some earlier function.

Not true. Not every function can be realized with just a small change
from what came before. If that were true, then evolution wouldn't
require millions of years. All that we see now could have evolved in
just a few thousand if the gaps between beneficial functions at all
levels were only a few residue changes from what came before.

At very low levels, you are right. Only a few changes are generally
needed. However, at higher and higher levels, you become less and less
right. The gap between what is currently in the genome and what might
be beneficial if it were ever found starts growing in a linear manner
with each increase in minimum size and specificity. Higher level
functions start to become very widely separated from everything around
them in sequence space. You just can't get there from here with just a
couple specific mutations anymore.

> Did you see the
> report about five point mutations that changed some protein such that
> before those five changes it was virtually useless at making the
> bacterium resistant to a particular antibiotic whereas after those five
> changes the resultant bacterium was very resistant to the antibiotic?
> (There was a numeric scale of resistance, which was only 0.05 at the
> start and 5000 after the five changes, approximately.)

Do you understand why this happened? The most common form of antibiotic
resistance evolution is based on disrupting the pre-existing
antibiotic-target interaction. If the target within the bacterium can
mutate so that the antibiotic can no longer bind as effectively to that
target as before, greater antibiotic resistance is achieved. This
turns out to be very easy to do. It is very easy to mutate something so
that what used to bind to it no longer binds as well. The ratio of
mutations that will produce this disruption to binding is very high -
at least as high as 1 in 20 and occasionally as high as 1 in 1 per
binding site residue position.

In short, it is much easier to disrupt a pre-established function or
interaction compared to producing a new function that is not based on
the destruction of some other function or interaction.

< this is all I have time for today >

Sean Pitman
www.DetectingDesign.com

Richard Forrest

unread,

Aug 26, 2006, 12:52:01 PM8/26/06

Seanpit wrote:
> Robert Maas, see http://tinyurl.com/uh3t wrote:
> > > From: "Seanpit" <seanpitnos...@naturalselection.0catch.com>
> > > The problem is, the driving forces of evolution, i.e., random
> > > mutation and natural selection, just can't create systems of function
> > > that require a minimum of more than a few thousand fairly specified
> > > bases of DNA.
> >
> > Why couldn't such a multi-thousand-base sequence for this "new"
> > function have evolved from some other sequence of comparable length
> > that coded some "old" function, requiring only five or ten changes from
> > the old sequence to the new sequence?
>
> This could happen, but the odds that the "old" function of equivalent
> length will only be 5 or 10 residue differences from the "new" aren't
> very good.

Unsupported Assertion #1

> I mean, you could win the lottery 5 times in a row - right?
> But what are the odds. The same thing is true of the odds that
> anything in the genome will be right next door to a new high-level
> system of beneficial function. And, by the way, a gap of 10 specific
> residues differences needed in a specific location is rather huge -
> requiring billions and even trillions of years to cross for an average
> sized population.

Irrelevance #1.

An argument based on a false premise, and a model which bear no
relationship to that proposed by biologists to explain such
evolutionary processes

>
> > > Of course an entirely new system doesn't need to evolve to detect
> > > such antigen changes! If you are talking about the evolution of the
> > > immune system, then no, I don't believe that the immune system evolved
> > > from ancestor creatures that didn't have an immune system.
> >
> > You seem to be claiming that the immune system itself was a *new*
> > system unrelated to anything that existed before. On what basis do you
> > make such a claim?
>
> The fact that the immune system as a whole is far too complex to have
> evolved from anything that is remotely likely to have existed before.

Unsupported Assertion #2. This is not a fact. It's an assertion.

> This is not to say that there are no sequence similarities with other
> proteins in other systems of function. However, these are based on
> common design, not common evolutionary ancestry.

Unsupported Assertion #3

"Common design", as has been pointed out by posters, is utterly useless
as an explanation for anything, having not basis in evidence whatsoever
either from design theory or biology. It's just a term you have made up
to gloss over the fact that common evolutionary ancestry is a sound and
exhaustively tested theory.

> The basis for this
> argument is both statistical

Unsupported Assertion #4.
As has been pointed out in considerable detail, your grasp of basic
statistics is so poor that your statistical arguments are nonsense.

> and demonstrable in real life.

Falsehood #1.
It simply is not demonstrable in "real life".

> There
> simply are no examples of any new function evolving that requires more
> than a few thousand fairly specified bp of DNA at minimum.

Unsupported Assertion #5.
As you have failed in spite of repeated requests to provide a measure
for "fairly specified", and reject out of hand the numerous examples
from biology of the evolution of novel functions without even
attempting to address the evidence, this unsupported assertion is
downright dishonest.

>
> > > The minimum coding requirement for a useful immune system is far too
> > > complex for evolutionary mechanisms to achieve even in trillions upon
> > > trillions of years of time.
> >
> > Let's do some arithmetic. Suppose about once every million years
> > there's a burst of adaption, whereby ten DNA bases are changed,
> > resulting in a new function different from before.
>
> The odds that 10 bp changes would hit upon a new beneficial high-level
> function are extremely remote.

Unsupported Assertion #6.

>
> > So over the course
> > of a billion years, one thousand of these bursts would accumulate,
> > totalling ten thousand DNA-base changes, i.e. virtually every DNA base
> > (in the multi-thousand sequence which now codes for the immune system)
> > would be different now from a billion years ago. That doesn't match
> > your claim that trillions of years would be required.
>
> It also doesn't match statistical likelihood.

Unsupported assertion #7.
This is based on your flawed model of evolutionary processes, which is
not one which any competent biologist would accept. Furthermore, your
grasp of statistics is so poor that any statistical argument you make
is full of flaws.

> Natural selection has
> the ability to maintain what is already in good working order. It
> doesn't have the ability to help random mutations find novel beneficial
> sequences before they are actually found by random mutations.

Irrelevance #2. No biologist has ever suggested that it does.

> The odds
> that ten random mutations will happen upon a new high-level function
> just aren't nearly as good as you seem to imagine.

Unsupported assertion #8.
Given your poor grasp of statistics and biology, why should anyone
believe you?

> You don't seem to
> understand the relative rarity of higher-level systems in sequence
> space.

You don't seem to grasp the fact that your model bears little
relationship to anything proposed by any biologist, and that your
arguments are utterly irrelvant.

> It's like hitting upon a particular atom in the entire universe
> after taking only 10 random steps. What are the odds of that? That is
> what you really need to ask yourself here.
>
> > > Duplicate genes or duplicate regions of a genome may indeed be many
> > > thousands or tens of thousands or even millions of bases in size. Yet,
> > > no new function is realized via a simple duplication of what was
> > > already there. The only thing duplication does is make two out of one.
> >
> > Correct so-far. But then one of the copies begins mutating toward new
> > functions, no longer required to do the old function because the other
> > copy can do it just fine.
> >
> > > We are talking about new functions here Marc - not more of the same
> > > thing.
> >
> > There's no such thing as *new* functions. Every function is a small
> > change (in DNA sequence) from some earlier function.
>
> Not true.

Falsehood #2.
It is true, and has been extensively verified by research.

> Not every function can be realized with just a small change
> from what came before.

Unsupported Assertion #9.

> If that were true, then evolution wouldn't
> require millions of years.

Unsupported Assertion #10.

> All that we see now could have evolved in
> just a few thousand if the gaps between beneficial functions at all
> levels were only a few residue changes from what came before.

Unsupported Assertion #11.

>
> At very low levels, you are right. Only a few changes are generally
> needed. However, at higher and higher levels, you become less and less
> right. The gap between what is currently in the genome and what might
> be beneficial if it were ever found starts growing in a linear manner
> with each increase in minimum size and specificity. Higher level
> functions start to become very widely separated from everything around
> them in sequence space. You just can't get there from here with just a
> couple specific mutations anymore.

Unsupported Assertion #12.

No matter how many times you repeat your flawed model, it won't become
acurate or realistic.

>
> > Did you see the
> > report about five point mutations that changed some protein such that
> > before those five changes it was virtually useless at making the
> > bacterium resistant to a particular antibiotic whereas after those five
> > changes the resultant bacterium was very resistant to the antibiotic?
> > (There was a numeric scale of resistance, which was only 0.05 at the
> > start and 5000 after the five changes, approximately.)
>
> Do you understand why this happened?

I suspect that he does rather better than you do.

> The most common form of antibiotic
> resistance evolution is based on disrupting the pre-existing
> antibiotic-target interaction. If the target within the bacterium can
> mutate so that the antibiotic can no longer bind as effectively to that
> target as before, greater antibiotic resistance is achieved. This
> turns out to be very easy to do. It is very easy to mutate something so
> that what used to bind to it no longer binds as well. The ratio of
> mutations that will produce this disruption to binding is very high -
> at least as high as 1 in 20 and occasionally as high as 1 in 1 per
> binding site residue position.
>
> In short, it is much easier to disrupt a pre-established function or
> interaction compared to producing a new function that is not based on
> the destruction of some other function or interaction.

Irrelevance #3.
So what?

>
> < this is all I have time for today >

If you are so short of time why are you wasting it on repeating the
same garbage over an over again on this forum?

Why not read Palaeobiology, especially the papers on taphonomy so that
you can understand why your assertion that rapid burial is required for
fossilisation is false?

Surely you don't want your web site to contain demonstrable falsehoods?

>
> Sean Pitman
> www.DetectingDesign.com

r norman

unread,

Aug 26, 2006, 1:38:27 PM8/26/06

On 26 Aug 2006 09:52:01 -0700, "Richard Forrest"
<ric...@plesiosaur.com> wrote:

>Unsupported Assertion #1 through #12

>Irrelevance #1 through #3

>Falsehood #1 and #2

You omitted the following:

Invalid Argument #1: Repeating unsupported assertions, irrelevancies,
and falsehoods again and again does not validate them, no matter how
strongly you assert them to be true.

Perplexed in Peoria

unread,

Aug 26, 2006, 3:46:02 PM8/26/06

"Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1156583677....@75g2000cwc.googlegroups.com...

I think you are exaggerating the difficulty here. To stay with the
words on a page analogy, it is difficult indeed to perform rearrangement
surgery on the page if the amount of white space between words is
only one letter wide. Easier if the typical amount of non-functional
white space averages ten letters or more. Your intuition is being
guided by modern proteins in which the amount of white space has
already been optimized down to one character.

Switching back to proteins, if you look at comparitive sequence data,
you will discover that the conserved functional domains of proteins
are frequently separated by variable-length spacer elements, whose
sequence is not strongly conserved by natural selection. At the
protein function level, the 'purpose' of these spacers is simply
to keep two functional units that 'ought' to stick together close
enough in space so that they have a good chance of making a more
intimate contact and actually sticking to each other as the protein
folds.

Actually, the situation may be more weasel/template-like than you
think. A big part of building a large biomolecular machine like a
flagellum is simply getting the pieces to stick together in a stable
way. In the evolution of stable 'lock and key' binding between
macromolecules, there is a kind of co-evolution, with the key acting
as a template for the lock and the lock acting as a template for
the key.

Check out, for example, what has happened in the co-evolution of
insects and flowering plants. My intuition is that quite elaborate
kinds of cooperative behaviors can be honed by NS. Of course, you
may well interpret this as just one more argument for design.

[snip remainder]

As I said at the outset, I never really wanted to get into a
discussion of the specifics. I am going to duck out now, and
leave you to your dialog with the quite competent Rick Norman.
Sorry if this seems like 'post-and-run'. You are, of course
welcome to the last word.

Perplexed in Peoria

unread,

Aug 26, 2006, 4:14:03 PM8/26/06

"Seanpit" <seanpi...@naturalselection.0catch.com> wrote in message news:1156583677....@75g2000cwc.googlegroups.com...

> Just show me were any new function has been observed to evolve - a
> function that requires at a few thousand fairly specified bp of DNA to
> code for it. You don't have to do the work yourself. Just show me a
> published paper describing such an observation.

Not exactly what you are looking for, but you may find it
interesting. I clip from something I posted on another thread:
-------------------------

> I showed him
> Matzke's paper on the evolution of the flagellum, but he says it does
> not meet his request because some of the jumps are too large (i.e,
> larger than a single mutation), and the evolutionary advantage of most
> of the steps was not explained. So what I am asking is- would it even
> be possible for evolutionary biologists to come up with the level of
> detail he is asking for? I mean to show the evolution of an IC system,
> mutation by mutation, with the advantage of each mutation and the
> likelihood of each mutation shown.

I don't think it would be possible for that to be done in the first
half of the 21st century. There are just too many steps to be
studied and too little funding. Maybe sometime in the next century,
someone will write a book doing exactly that (and no one will read it).

However, the following paper does show the kind of thing that
is possible today. It is not evolution of an 'IC' system - it is
something much simpler, but it is still the kind of thing (a change
in protein topology) that one might think evolution would find
difficult to do. And they not only specified step-by-step and
mutation-by-mutation how the protein must have evolved, they
then went ahead and evolved it under artificial selection.
------
Nature Genetics 38, 168 - 174 (2006)
Published online: 15 January 2006; | doi:10.1038/ng1717

Evolution of new protein topologies through multistep gene
rearrangements

Sergio G Peisajovich, Liat Rockah & Dan S Tawfik

Abstract:
New protein folds have emerged throughout evolution,
but it remains unclear how a protein fold can evolve
while maintaining its function, particularly when fold changes
require several sequential gene rearrangements. Here, we
explored hypothetical evolutionary pathways linking different
topological families of the DNA-methyltransferase superfamily.
These pathways entail successive gene rearrangements
through a series of intermediates, all of which should be
sufficiently active to maintain the organism's fitness. By
means of directed evolution, and starting from HaeIII
methyltransferase (M.HaeIII), we selected all the required
intermediates along these paths (a duplicated fused gene
and duplicates partially truncated at their 5' or 3' coding
regions) that maintained function in vivo. These intermediates
led to new functional genes that resembled natural
methyltransferases from three known classes or that belonged
to a new class first seen in our evolution experiments and
subsequently identified in natural genomes. Our findings
show that new protein topologies can evolve gradually through
multistep gene rearrangements and provide new insights
regarding these processes.

Abstract and Full Text Links at Nature Genetics
http://www.nature.com/ng/journal/v38/n2/abs/ng1717.html

z

unread,

Aug 27, 2006, 1:38:06 AM8/27/06

On 26 Aug 2006 01:55:59 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

>
>z wrote:
>
>< snip >
>
>> >> You miss the point. There is a huge amount of structural information
>> >> required to "specify" an enzymatic cascade. The active site of each
>> >> enzyme must recognize both the substrate and the product of the
>> >> reaction.
>> >
>> >That's true. Each individual enzyme in a cascade may indeed require a
>> >great deal of specific order to its individual residues relative to
>> >themselves within that enzyme. However, the overall function of the
>> >enzymatic cascade does not require the additional requirement that each
>> >individual enzyme be specifically arranged in 3D space relative to all
>> >the other enzymes. A flagellar motility system does have this
>> >additional specificity requirement - which makes an exponential
>> >difference in the rarity of such a system in the potential of sequence
>> >space.
>>
>> Only if you require selection to act all at once. Cooption is the
>> most likely route to getting to a flagella.
>
>It doesn't matter how you get there, the final result, the flagellar
>motility system, requires a rather large minimum part and specificity
>requirement. It doesn't matter if you got there by co-opting previous
>systems via evolutionary mechanisms or straight up de novo intelligent
>design. The final product requires a minimum number of residues to be
>arranged in a pretty specific way.

In a sense, so does a pile of sand.

>
>This is not true of an enzymatic cascade. No matter how such a cascade
>is created, it does not require that all of its individual protein
>parts, no matter how much they are individually specified, to be
>specifically arranged relative to each other. This creates an
>exponential difference in rarity within sequence space in comparison
>with a flagellar motility system - the odds of obtaining all the needed
>parts in the proper order.
>
>Again, for example, it is much much easier to throw two double sixes
>compared to throwing two double sixes in a row.

Again, I think you miss the point. An ezyme cascade requires a huge
amount of protein surfaces to work properly. It makes no difference
whether the enzymes contact each other or not. The active sites have
to match up to the cognate substrates and products.

>
>> >You need to talk to Marc about antibody evolution. Marc says that
>> >antibody evolution doesn't count as real evolution. But, that is Marc
>> >for you. Personally, I agree with you that improvement in antibody
>> >specificity over time, via random mutation and function-based
>> >selection, is indeed real evolution in action. However, there is just
>> >one little problem with this sort of evolution.
>> >
>> >The problem with antibody evolution is that it is template-based. All
>> >that has to happen is for a very small change in the antibody sequence
>> >to result in a better match to a pre-established non-self antigen
>> >sequence for a selective advantage to be realized. The odds of an
>> >improved binding match to a pre-established template being realized are
>> >actually quite good.
>>
>> If you are refering to protein templates, you are way off base here.
>> Antibodies are semi-randomlly made- there are a huge number of
>> potential sequences possible for the CDR's, but it is non-infinite.
>> Something on the order of 10^20 theoretically, with about 10^12 or so
>> actually used.
>
>There certainly are a large number of pre-formed antibody sequences
>before the virgin immune system is ever exposed to a foreign antigen.
>
>> There is no such thing as a "pre-established non-self antigen",
>
>Any foreign antigen that enters the immune system is pre-established
>before it meets the immune system. The immune system is able to
>respond with greater force and specificity against the same antigen
>with repeated exposure.

So "pre-established non-self antigen" was meant to be a synonym for
"foreign"?

>
>> and
>> you will make self-reactive antibodies all the time. In a very simple
>> sense, self-reactive B cells are spanked on the nose and not given a
>> cookie. The eventually die (mostly- autoimmune disaases are the main
>> exception). B cells that do respond to a foreign antigen AND don't
>> respond to self are given a cookie and undergo a process (in mammals)
>> of what is known as somatic hypermutation. They actually mutagenize
>> their recombined antibody genes.
>
>That's right . . .
>
>> However, there is no guidence to the initial recombination events that
>> determine whether or not a B cell makes an antibody that rocognizes a
>> target.
>
>Correct . . .
>
>> If that doen't happen, then bad things might happen. Then
>> again, the innate and/or cell mediated bits of the immune system do a
>> pretty fair job.
>
>Against certain types of invaders . . .

Actually, it's impressive what it can do. Patients who take Rituxan
to treat B-cell lymphomas are pretty much completely devoid of normal
B-cells as a result. There are surpassingly few side effects related
to infection given that.

I agree, and am confused by your arguments towards other systems. You
have no problem with small sequence changes in an antibody that can
increase affinity for an antigen, but you fiind the idea that this can
occur for other proteins to be impossible.

>
>Now, compare this with the problem of evolving a function like
>flagellar motility. Where is the template here where one or two
>residue changes will produce an improvement in flagellar motility
>before flagellar motility is even achieved yet? - or any other
>beneficial steppingstone function? There simply is no template to base
>such small changes on in a selectable way. That's the problem.
>Antibody-antigen matching evolution is like Dawkins' "Methinks it is
>like a weasel" algorithm. Flagellar evolution cannot work like this.

I'd assume that the starting point was a rotary enzyme system that
coupled proton flow to some other function- much like the F1-F0
ATPase. Nobody is arguing that it all came about as one grand event
from scratch.

This paragraph clearly states that you can only see a flagella as
popping up all at once. And yes, you can have protein sequence
changes that are neutral. It's protein dependent, and also skewed
towards residues found at the surface of the molecule.

>
>> >> Your body can in a span of a few weeks produce an antibody to almost
>> >> any foreign protein. Real time protein evolution in that the
>> >> resulting antibody will contain sequences that are different from
>> >> anything in your germ line.
>> >
>> >That's true, but it's all based on template matching . . .
>>
>> The selection is at the anigen-antibody level. So when does
>> protein-protein interaction deviate from "template matching" from your
>> definition.
>
>The ratios are very different. The ratios are very high for an
>antibody to match better with an antigen. The ratios are much much
>lower for matching a proto-subsystem to another subsystem to produce a
>flagellar motility system. First off, the antibody already binds to
>the antigen in a selectable way to begin with. The only thing that
>"evolves" in this case is an improvement to the same binding function.
>It is easy to improve a function once you already have it. It is quite
>another thing to evolve the function to begin with when you don't have
>it at all.

Actually, affinity maturation produces antibodies that vary randomlly
WRT affinity to the antigen. You can easily get antibodies out that
have essentially no affinity to the target. A single amino acid
change can make an Ab with sub nM affinity go to nothing detectable.

And what you call "template matching" is just another word for
selective pressure. In this case it's very easy to define and
quantitate.

As far as starting from nothing, no biologist thinks that the flagella
started from scratch.

>
>> >> Protein-protein interactions are easy to evolve. While ther are
>> >> examples of proteins that actually swap bits of secondary structure to
>> >> form quaternary structure, for the most part it's just two surfaces
>> >> sticking together. You fixate on this as if it's a big deal-
>> >> something that caused me to scratch my head and wonder why. Getting a
>> >> protein to recognize a small moleule and actually do something with it
>> >> is far trickier.
>> >
>> >For a single protein - yes. However, when you starting talking about
>> >dozens of specific proteins needing to stick to each other in very
>> >specific ways, the statistics involved start really adding up. We
>> >aren't just talking about simply getting one protein to stick to
>> >another in just any old way. We are talking about dozens of proteins
>> >sticking to each other in a very specific way that cannot be built up,
>> >one tiny residue change at a time, via template-type matching.
>>
>> Well, practically speaking, you are talking about a structure that is
>> made up of roughly a dozen proteins.
>
>The flagellar motility system is made up of a minimum of over 20
>proteins - but that is beside the point.

We are picking nits here- not all the proteins are actually part of
the structure and not all are essential. We are within an order of
magnitude here :)

>
>> Most of the protein-protein
>> interactions in that structure are self-interactions. There are
>> critical non-self interactions involved but it's not as complicated as
>> you make it out.
>
>Oh really? The interactions of the 20+ different protein parts isn't
>as complicated or "specified" as I make it out? Tell me, which one of
>these interactions isn't really needed?

Notice I did say there were"critical non-self interactions" and did
not say anything about interactions not beeing needed. What I did say
was I think you are overestimating the complexity of the problem from
a protein-protein interaction POV.

>
>> >Where have you or anyone else shown that the simpler subsystems you
>> >proposed can be easily stuck together in just the right way to reach
>> >the next beneficial steppingstone function in your proposed pathway
>> >with just a handful of residue changes? You make these bald claims
>> >that such a detailed description has been delivered, but this is just
>> >hot air. Where is this description? I have yet to read anything of
>> >the sort.
>>
>> Evolution does not plan for the future and bacteria don't make genome
>> back-ups for us to look over. We do have examples of cooption in your
>> favored system. The T3SS of some eubacterial parasites of eukaryotes
>> is either A) a cooption with specialization from the flagellare T3SS
>> or B) an evolutionary relic of an independant system that was coopted
>> by the flagella. A parses best given the restricted range of
>> organisms that we have noted it in. The caveat is that the range of
>> organisms that his been observed in are organisms are of special
>> interest because they are pathogens.
>
>It is strange that the TTSS system is so commonly touted as the most
>likely starting point by many evolutionists since the TTSS system is
>supposed to have evolved hundreds of millions of years after flagellar
>evolution. Many argue that there is good evidence to believe that the
>TTSS starting point arose from the fully formed flagellum and not the
>other way round.

I did note that as my point A.

>
>Consider that the bacterial flagellum is found in both mesophilic,
>thermophilic, gram-positive, gram-negative, and spirochete bacteria
>while TTSS systems are restricted to a few gram-negative bacteria. Not
>only are TTSS systems restricted to gram-negative bacteria, but also to
>pathogenic gram-negative bacteria that specifically attack animals and
>plants . . . which supposedly evolved billions of years after flagellar
>motility had already evolved! Beyond this, when TTSS genes are found
>in the chromosomes of bacteria, their GC (guanine/cytosine) content is
>typically lower than the GC content of the surrounding genome. Given
>the fact that TTSS genes are commonly found on large virulence plasmids
>(which can be easily passed around between different bacteria), this is
>good evidence for horizontal transfer to explain TTSS gene
>distribution. Flagellar genes, on the other hand, are usually split
>into 14 or so operons, they are not found on plasmids, and their GC
>content is the same as the surrounding genome suggesting that the code
>for the flagellum has not been spread around by horizontal transfer.

Also note that the flagellar structure that we are discussing is also
restricted to gram negative organisms. And flagellar genes are also
associated with pathogenicity islands in some pathogens, indicating
that they were also aquired by horizontal transfer.

Personally, I think the strongest evidence for the argument that the
T3SS system is derived is that it is only found in bacteria that are
parasites or commensals of eukaryotic cells.

Nice example of cooption however.

Been down this road before with spintronic. It's ugly biochemically
from a technical POV and a paleantology POV. Molecules don't leave
infomative fossils for this question But we do have a system where we
have RNA acting as an informational molecule (mRNA), an adaptor
(tRNA), as a structural RNA (most of the ribosome), and as an enzyme
(the peptidyl transferase). It does give me an idea where to look for
a precursor system.

>
>> Trascription - bring on your examples.
>
>Again, describe to me how the function of transcription could have
>evolved. It is very complicated. Please explain to me how such a
>complex system could have evolved one little step at a time . . .

Transcription can be baroquely complex, or beautifully simple
depending on the system you are looking at. I was asking you to toss
one out.

>
>> Pinocytosis is laughably easy mechanically.
>
>Oh really? Laughably easy mechanically? Hmmmm . . . please do explain
>to me how such a laughably easy system could have evolved - step by
>mutational step.

Pinocytosis is simple- you just need to induce curvature of the
phospholipd membrane. There a huge number of proteins that can do
this. You can even do this crudely with the use of specific
phsopholipases. I think you probably meant endocytosis.

>
>> Basic vision systems are
>> also easy, but non-essential.
>
>The most basic vision systems are enormously complex. They are not
>anywhere near "easy". Do you have any idea what's involved in order
>for the most basic vision function to be realized?

>Even a simple light sensitive spot is extremely complicated, involving
>a large number of specialized proteins and protein systems. These
>proteins and systems are integrated in such a way that if one were
>removed, vision would cease.

I would offer that light sensitive spot is rather simple. They exist
in single cell organisms and are pretty much based on a localized
patch of ion channels with a light sensitive pigment bound.

>
>For example, the first step in vision is the detection of photons. In
>order to detect a photon, specialized cells use a molecule called
>11-cis-retinal. When a photon of light interacts with this molecule,
>it changes its shape almost instantly. It is now called trans-retinal.
> This change in shape causes a change in shape of another molecule
>called rhodopsin. The new shape of rhodopsin is called metarhodopsin
>II. Metarhodopsin II now sticks to another protein called transducin
>forcing it to drop an attached molecule called GDP and pick up another
>molecule called GTP. The GTP-transducin-metarhodopsin II molecule now
>attaches to another protein called phosphodiesterase. When this
>happens, phosphodiesterase cleaves molecules called cGMPs. This
>cleavage of cGMPs reduces their relative numbers in the cell. This
>reduction in cGMP is sensed by an ion channel. This ion channel shuts
>off the ability of the sodium ion to enter the cell. This blockage of
>sodium entrance into the cell causes an imbalance of charge across the
>cell's membrane. This imbalance of charge sends an electrical current
>to the brain. The brain then interprets this signal and the result is
>called vision. Many other proteins are now needed to convert the
>proteins and other molecules just mentioned back to their original
>forms so that they can detect another photon of light and signal the
>brain. If any one of these proteins or molecules is missing, even in
>the simplest eye system, vision will not occur.

That certainly is not the simplest system and you know that. Single
cell organisms most certainlly don't have brains.

>
>The question now of course is, how could such a system evolve
>gradually? All the pieces must be in place simultaneously. For
>example, what good would it be for an earthworm that has no eyes to
>suddenly evolve the protein 11-cis-retinal in a small group or "spot"
>of cells on its head?

Retinal is not a protein, it's a beta carotene derivative. A bell
should be ringing about now....

>These cells now have the ability to detect
>photons, but so what? What benefit is that to the earthworm? Now,
>lets say that somehow these cells develop all the needed proteins to
>activate an electrical charge across their membranes in response to a
>photon of light striking them. So what?! What good is it for them to
>be able to establish an electrical gradient across their membranes if
>there is no nervous pathway to the worm's minute brain? Now, what if
>this pathway did happen to evolve and such a signal could be sent to
>the worm's brain. So what?! How is the worm going to know what to do
>with this signal? It will have to learn what this signal means.
>Learning and interpretation are very complicated processes involving a
>great many other proteins in other unique systems. Now the earthworm,
>in one lifetime, must evolve the ability to pass on this ability to
>interpret vision to its offspring. If it does not pass on this
>ability, the offspring must learn as well or vision offers no advantage
>to them. All of these wonderful processes need regulation. No
>function is beneficial unless it can be regulated (turned off and on).
>If the light sensitive cells cannot be turned off once they are turned
>on, vision does not occur. This regulatory ability is also very
>complicated involving a great many proteins and other molecules... all
>of which must be in place initially for vision to be beneficial.

Nice set of strawmen. However, you have failed to notice that there
are huge numbers of G-proteins, with the vast majority having nothing
to do with vision. Earthworms do have G=protein coupled receptors in
their nervous system so the basic biology for resetting the signal is
there.

>
>> Vascular systems- plants or animals?
>
>Both . . .

I was being facetious. The vascular system of plants share
commonality in name and that they are tube like.

>
>> Gonna be hugelly different, and I don't know much about plants,
>
>Both are at a fairly high level of functional complexity.

Tubes are fairly simple, yet plants and animals seem to use different
mechanisms to make them. I suppose it comes down to which tube you
are interested in.

>
>> ATP synthesis can be done a bazillion
>> different ways- are you asking why ATP?
>
>A "bazillion" different ways there may be, but this just isn't enough.
>The ratio of ways that will work compared to those that won't is
>extremely tiny. It can only be done with the use of a relatively
>limited number of very specific arrangements of a rather large number
>of protein parts associated with the cellular membrane in very specific
>ways. This translates into a very tiny portion of sequence space that
>could actually give rise to an ATP producing system that is actually
>beneficial by the time it happens to come on the scene.

No, you said that ATP synthesis was a specified system. I am merely
pointing out that there are a huge variety of ways that organisms can
make and use ATP. This indicates that there is a huge portion of
sequence space that can be sampled to make an ATP generating system.

If we are talking about substrate level ATP sysnthesis from sugars,
then there are 2+ main ways to do this (dpends on how many different 5
carbon pathways you feels are distinct). But most organisms don't
live on sugars so that's only a tiny subset of metabolic pathways.

B Miller

z

unread,

Aug 27, 2006, 2:36:49 AM8/27/06

On 26 Aug 2006 08:35:21 -0700, "Seanpit"
<seanpi...@naturalselection.0catch.com> wrote:

So birds using gene conversion as opposed to somatic hypermutation for
Ab diversity is s designed element?

>
>> How is it different from
>> taking an existing ATPase and using it to make something like the
>> flagellar motor?
>
>Because, the function of the flagellar motor is not there originally
>like it is for the antibody binding. There is no ATPase that has even
>a little bit of the flagellar motility function to start out with.
>There is no template upon which to build up the flagellar motility
>system one tiny mutation at a time. All these are significant
>differences that produce the gap problem for evolution.

The fact that both the F1-F0 ATPase and flagella use the same power
source to spin and share some sequence homology soen't make you
curious? We would have a gap problem if the flagella was the only
thing that used PMV to drive a rotary engine.

>
>> You make these assertions, but you can't back them
>> up. Why do you think that the assertions are worth anything?
>
>I've shown you example after example. The evidence in literature is
>overwhelming. Evolution of functions that cannot use a template just
>doesn't happen beyond very low levels of functional complexity - i.e.,
>those functions that require a minimum of more than a few thousand
>fairly specified bp of DNA. There's not a single example of such a
>thing happening in real life nor is this notion statistically tenable
>on paper.

In other words, Seanpit cannot imagine selection unless it's a
physical object (template). His specification requirement is
spcecious, at best.

>
>> > The odds that a particular antibody mutation will result in an improved
>> > binding to the antigen are quite high. That is why antibody evolution
>> > happens so rapidly. The problem is that not all functions can evolve
>> > this way - with the use of a template. For example, the flagellar
>> > motility system cannot evolve one residue change at a time via template
>> > matching. There simply is no series of beneficial steps that are
>> > separated by only one or two residue differences in the pathway of
>> > flagellar evolution.
>>
>> How high are they and why are they different from any other protein
>> function?
>
>The odds that a mutation will result in improved antibody-antigen
>binding, when the initial binding isn't the most ideal, are extremely
>good - perhaps as high as 1 in 2 or 3 mutations to begin with.

Nope, not even wrong. Seanpit is assuming that there is something
magical happening that makes Ab affinity maturation different, and you
can get "perhaps as high as 1 in 2 or 3 mutation" to get higher
affinity. Affinity maturation results in random changes to Ab
affinity. Selection picks the winners, just like in the biosphere.

>
>The reason for this is the same reason why Dawkins' "weasel" program
>works so well. Every single character in a random sequence that gets
>mutated to match the template is selected for improved reproductive
>fitness. In this particular example, the odds that a mutation will
>change a character that isn't "right" to the correct type of character
>for that position is no less than 1 in 27. Those are extremely good
>odds and result in very rapid evolution of a random sequence to "match"
>the template sequence.

Affinity maturation is much longer odds per event than 1:27. There
are still febates ongoing over the transversion to transition bias,
but let us just focus on the CDR's and allow two base changes. We are
talking about roughly 2^60 potential sequences.

BTW, affinity maturation is not limited to the CDR's, and obviously
not all of the sequence space is sampled due to biological constraints
(no organism can live that long).

>
>Now, when it comes to the flagellar system, there is no template with
>which to compare every single residue difference and select every
>single residue change as an improvement or a detriment. Without this
>template, the finding of the next beneficial steppingstone starts to
>involve more and more non-beneficial changes. And, this gap of
>non-beneficial changes grows linearly with each increase in the minimum
>size and specificity requirement of the functional system. A linear
>increase in these minimum requirements translates into an exponential
>increase in the random walk/random selection time needed before success
>can be realized - on average.
>
>> Since you can't demonstrate that any other protein sequence
>> isn't just as plastic and variable when it comes to doing things, what
>> is your beef?
>
>Oh, but I can. Do you realize that every single antigen will have at
>least some match to an antibody of a well-working immune system?
>Consider then your notion that all other systems of function will be
>just as easily found by looking at a really simple one that is not
>based on template matching - like the lactase function. Many types of
>bacteria simply cannot evolve the relatively simple lactase function
>despite high mutation rates and a high selective advantage if the
>lactase function were ever realized. Some bacteria have been observed
>to be lactase negative for over 40,000 generations of time in specific
>experimental conditions. Others have been lactase negative for over 1
>million generations according to hospital logs.

No, you cannot have every single immune system respond to every
possible antigen.

Observation of lactase negative for 1 million generations does not
mean that they have been under selection for lactase for 1 million
generations. As a matter of fact, they have not been. That's like
saying that "I have observed a million dogs, and none fly. Therfore
mammals can't evolve flight".

>
>Scientists like Barry Hall have referred to these bacteria as having
>"limited evolutionary potential". Now Ron, what is it, exactly, that
>limited the evolutionary potential of these bacteria? What made them
>incapable of evolving the lactase function despite the significant
>advantage that they would have gained if they were able to do so?

Limited evolution for lactase in isolation, full stop. Not that they
have limited evolutionary potential in toto.

>
>The fact is that if anything in the bacterial genome of these limited
>bacteria were just one or two residue changes away from the lactase
>function, the lactase function would have evolved - and quickly. We
>know this because such an experiment has been done and was successful.
>So, the fact that many types of bacteria cannot evolve the lactase
>function can only mean one thing. There is a larger gap between what
>they have and the minimum requirements of the relatively simple single
>protein lactase function.

You do realize that lactose does not freely diffuse across the cell
wall of E coli? The effective concentration of lactose in the cell
population was damn near zero, so there was no selectice pressure for
a lactase (for the confused folks, lactase is an older term for
beta-galactosiase or beta-gal).

Considering that most of evolutionary gentics is statistically based,
that particular argunent is a bit weak.

>
>> This is just sad and at some level you know it. If creationist like
>> yourself had valid arguments we would all know about it by now. Get a
>> clue and get some help. I can't believe that there isn't someone that
>> you trust that can set you straight about this. It is black and white
>> that you have been scammed. If it wasn't Dover and Ohio would have
>> totally different outcomes.
>
>Not true. The ToE isn't just a cold rational "scientific" notion. It
>is believed with a strong passionate faith by the mainstream scientific
>community. It has taken on religious devotion. Such devolution is not
>easily overcome - even by the strongest rational scientific evidence to
>the contrary.

Au contraire- we are talking Nobel if you can disprove it. I am a
scientist- we are the most contrary folk. We make our names on
finding new stuff, so if the ToE was in any way observationally weak
we would find it.

>
>> > > What an idiot, or is it simple dishonesty this time?
>> >
>> > Well, I can assure you that I'm being quite honest in these threads.
>> > So, I guess I'm left with the "idiot" option? ; )
>>
>> Basically, you are worse off then an idiot. The insanity defense is
>> about all you have left.
>
>LOL - bummer ; )
>
>>You are too far gone for it to be simple
>> incompetence at this point, and at some level you probably know it. Do
>> you want me to quote your defense of ID when you claimed that you could
>> do better than the rubes that ended up taking the replacement scams
>> from the guys that you still think have valid arguments? Do you still
>> think that you could do better than the ID scam artists did in Ohio and
>> Dover?
>
>Actually I don't think the outcome would have been any different if I
>had presented my ideas in Ohio or Dover. I think this whole thing is
>far beyond rational presentation of ideas. It is about one religion
>vs. another. And yes, the ToE is held with just as much passion,
>fervor and faith by you guys as any religious belief.

Actually, there is a fair bit of difference. To a scientist, being
wrong is a fact of life. To paraphrase the Red Queen, if I've had a
half a dozen wrong ideas before lunch means that I've had a good start
on the day. Not so true for a relegious figure, I'd bet.

>
>> If you do, why don't you consider that to be insanity? Just
>> think if it was someone else. Get someone you trust to clue you in,
>> and if you want to claim honesty and integrity, put up front on your
>> web page that even you don't trust the junk in it. If you trusted it
>> you would be able to demonstrate that it means what you think, and if
>> you could do that we wouldn't have any arguments.
>
>There is a big difference between presenting very good evidence and
>getting someone else who is strongly biased against it to accept it for
>what it really is. You can only lead a horse to water you know . . .

"you can lead a house to order, but you can't make it think".
Homilies are good fun.

>
>And, remember Ron, many very good ideas were scoffed to scorn
>originally by the mainstream scientists of the day. Be careful when
>you call someone an idiot or insane. Sometimes, these "crazy" people
>are actually right after all.

What is the DSM term(s) for someone who imagines that the world was
created for them? And how do you differentiate between the sifferent
pathologies?

B Miller

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