Shakespeare and the Chicken Egg
Sean Pitman
> It is far from clear that there is any difference between the kind of
> process which generates a chicken from a chicken egg and the kind of
> process which allows William Shakespeare to write "Hamlet".
Oh really? Hmmmmm . . . Do you really think that the chicken egg was
as creative it its forming of the chicken as Shakespeare was in his
forming of Hamlet? For example, a computer can be programmed to do
fantastic things, but it is not creative. Now granted, the terms
"intelligence" and "creative" have not yet been absolutely defined and
maybe they never will be. However, they are defined enough for us to
know that human intelligence can do things that computers and eggs
cannot do. Humans can create new things at high levels of functional
complexity that we never created before and were not preprogrammed to
create automatically. An egg or a computer program cannot create new
things that they were not already programmed to create. A chicken egg
cannot make anything except for a chicken. Shakespeare, on the other
hand, was not preprogrammed to make Hamlet or Macbeth or the Taming of
the Shrew. Though these creations are admittedly not as functionally
complex as a chicken, the process involved in their creation was much
more creative. If Shakespeare had figured out how to make a chicken
without some sort of internal preprogramming, then that would have
been very creative indeed. The fact of the matter is, just because a
computer can do something better or even at a higher level of
complexity than you can do does not make the computer more creative
than you are. Wouldn't you agree that this is a significant
difference between Shakespeare and the chicken egg?
>You are
> merely presuming your conclusion when you say that "no such mindless
> process can give rise to a greater level of complexity... that goes
> very far beyond what its original programming allowed it to do".
This conclusion happens to be my hypothesis. That is what the
scientific method is all about. You observe a given phenomenon and
then make a conclusion/hypothesis to explain this phenomenon. This is
a valid scientific process as long as the hypothesis makes a testable
prediction that can in fact be disproved or "falsified". This is what
I have done. I have predicted that no mindless process will ever be
able to create anything new within a given level of complexity or
beyond in real time. I have drawn this line at several thousand amino
acids working at the same time. So far, the highest level of
functional complexity that has been observed to evolve in real time
requires less than a few hundred amino acids at minimum for that type
of function (i.e., the lactase or nylonase functions). Nothing beyond
such levels of complexity have ever been shown to evolve in real time
and even many life forms seem to be incapable of evolving much of
anything requiring only a few hundred amino acids working at the same
time. For example, many types of bacteria, to include Hall's double
mutant E. coli bacteria, cannot evolve the relatively simple lactase
function in over a million generations of positive selection pressure.
Hall himself referred to these bacteria as having, "limited
evolutionary potential." Now I find that most interesting . . .
> The
> statement itself attempts to confuse the issues by using a term which
> we normally associate with human effort (namefly 'programming') with
> something that seldom does (namely biological development).
Biological development certainly involves pre-established information
systems of extraordinary informational complexity. Without this
information being there fully formed, random organic matter doesn't
turn into much of anything besides amorphous ooze, much less a
chicken. The pre-established information system is vital to the
functional organizational ability of the chicken egg . . . and all
other biological activities. For example, the parts of a flagellum,
if added to solution suddenly or randomly, will not self-assemble. A
very specific order and concentration of part additions is required in
order for the flagellum to form in such a way that its motility
function will be realized. This specific order requires a
pre-established information system and physical apparatus to decode
this information before a motile flagellum can be built. Information
systems at such levels of complexity simply do not self-assemble
without outside input from some higher information system or
intelligence.
<snip>
> This may be what you think the problem is in a nutshell, but it
> unfortunately has no evidence to back it up at all.
What would you call the fact that there is a ladder of complexity
where evolution works very well on the lowest rungs, but less and less
well as it tries to move up the ladder to higher levels of functional
complexity (involving more and more amino acids at minimum)?
For example, very simple functions, such as many forms of antibiotic
resistance, which work by blocking or interfering with other
pre-established functions or interactions, evolve commonly and
rapidly. This is because there are many different ways, involving
only one or two point mutations, to interfere with the
antibiotic-target interaction. So, there are a lot of beneficial
sequences surrounding the starting sequence. Like stepping-stones,
the mindless evolutionary processes of random mutation and natural
selection can quickly cross over toward the move beneficial levels of
more and more efficient antibiotic resistance. However, functions
that require independent action, as is the case with enzymatic
functions, are much more difficult to evolve since there are far fewer
ways for a series of amino acids to achieve a particular enzymatic
function. Still, those enzymatic functions that require fewer amino
acids at minimum in the least specified order are the easiest ones to
evolve. In fact, although there are far fewer examples of novel
enzymatic functions evolving, they are still fairly common - and more
common for shorter enzymes. However, for those functions that require
more and more amino acids, at minimum, working together at the same
time in a fairly constrained manner, evolution becomes exponentially
less and less common. In fact, many life forms, such as many types of
bacteria, simply cannot evolve something like a relatively simple
lactase function, which requires, at minimum, only 400 or 500 amino
acids in a fairly flexible order.
Some in this forum, such as Von Smith and a few others, have suggested
that the ratio of lactase to non-lactase sequences at this level of
complexity is as high as 1 in 1,000 sequences. The problem here is
that Von clearly doesn't understand the power of random walk. If the
ratio were truly this high, only 1,000 mutations would be needed, on
average, to find a lactase sequence in sequence space. An average
bacterial colony would realize such a sequence many its members in
just one or two generations. Evolution at such a high ratio for
success would not only be guaranteed, it would be rapid. The fact is
that E. coli, without the lacZ and ebg genes, do not evolve the
lactase function despite tens of thousands of generations under high
selection pressures, high mutation rates, and very large population
numbers. Other bacteria haven't evolved this function either in over
a million generations of time - and Von thinks that the ratio is 1 in
1000? Please! You've got to be kiddin me!
The problem is that at increasing levels of minimum amino acid
requirements, the ratio of beneficial vs. non-beneficial goes down
dramatically so that not only can no new types of functions be evolved
at higher levels of complexity, they cannot be evolved even within the
same level of complexity. It is like the diagram figured below where
simple beneficial islands are clustered close together, but get
farther and farther apart as one moves up the ladder of complexity
(each dot represents a beneficial sequence in sequence space).
_______________________________________
…………………………………………………..
. . . . . . . . . . . . . . . . . . . .
. . .
. . . . . . . . .
.
. . . .
.
. . .
.
.
.
> Your conclusion of
> an intelligent designer is based upon the improbability of long chains
> of amino acids forming randomly, but that's rather silly and bears no
> resemblance to any modern theory of evolution/abiogenesis/genetics.
Actually that is exactly what the theory of evolution suggests.
Random mutations are supposed to find new beneficial functions, which
can be selected in a positive way by Mother Nature.
> The truth is that long chains of amino acids in very specific sequences
> DO form, form with great frequency.
Actually they do not form with great frequency outside of the
pre-established information system in the DNA of that creature which
codes for their formation.
> If you are to claim that they are
> somehow designed, it is up to you to present evidence that they are
> designed. Merely asserting that some particular model of random formation
> makes them exceptionally unlikely is not sufficient.
Actually it is sufficient. The detection of intelligent activity at
the level of humans or beyond is based on two things: 1) That such
levels of intelligence are capable of producing a given phenomenon,
and 2) that no lesser intelligence or other mindless process is
capable of producing anything even close. Once these two things are
known, intelligent design can be reasonably inferred with a very high
degree of predictive value.
Also, I've done a lot more than just assert than the success of a
random walk will be unsuccessful at a certain level of functional
complexity (involving a few thousands amino acids at minimum), I have
demonstrated a real-life exponential decline in the ability of
mindless evolutionary processes to produce new types of functions at
higher and higher levels of complexity. I have also proposed a very
reasonable explanation for this decline in ability found in the form
of a neutral gap problem. Each additional minimum amino acid
requirement expands the sequence space 20 fold. However, the number
of beneficial sequences only expands a fraction of this amount. This
creates an exponential decrease in the ratio of beneficial vs.
non-beneficial sequences in sequence space. The stepping-stones
become more and more widely separated on average. Very soon the
average gap between beneficial stepping-stones is truly enormous. The
only way for the mindless processes of evolution to bridge this gap is
via random walk alone since nature cannot select between equally
non-beneficial sequences even though they may be different in amino
acid "spelling".
Sean
Deaddog
"Sean Pitman" <seanpi...@naturalselection.0catch.com> wrote in message
news:80d0c26f.03120...@posting.google.com...:
> I have predicted that no mindless process will ever be
> able to create anything new within a given level of complexity or
> beyond in real time. I have drawn this line at several thousand amino
> acids working at the same time.
Well, um, who gives a rat's ass? You can define it to be 'my big floppy
friend the scarecrow' for all I care. A strawman is a strawman is a
strawman. No one claims that complex enzymatic functions arose with great
alacrity from long strings of random protein sequence information. This has
of course been tested: Keefe and Szostak (2001), Nature 410:715 (the enzyme
work has yet to appear, though). High-affinity binders similar to modern
catalysts don't occur frequently (although if I read your argument
correctly, you would have predicted not at all?). Duh. These experiments
are cool but not necessarily relevant to origins, and certainly not relevant
to understanding modern protein evolution, which as we have previously
stated and as you have previously ignored occurs in a wonderfully modular
fashion that allows high order complexity to be achieved.
Similarly, your attempts to squish Hall's most excellent experiments on the
evolutionary potential of cryptic sequences into some sort of diatribe on
design are just ... weird. If you want to tilt at windmills, at least have
the good sense to trade in your wheelbarrow for a horse, your pixie stick
for a lance, and your intellect for ... well, we shouldn't move outside the
realm of possibility.
On the other hand, many people would claim that simple enzymatic functions
that could support relatively limited metabolisms evolved at one point, and
that more complex function arose from duplication and diversification of
these simple functions. There is an abundance of evidence to support this
non-strawman theory of enzyme function and metabolic origins. For example,
simple peptides are more than capable of acting as catalysts. A former
advisor used to chortle that lysine is a kick-ass oxaloacetate
decarboxylase, and it is. And the formation of protein structure, the
precursor to common catalytic function, is also surprisingly easy. I think
one of the best papers in this regard is Kamtekar et al. (1993), Science
262:1680. Basically, even very simple codes based on very simple
physicochemical models can lead to the formation of coherent protein
structures. Follow-up work by the Hecht lab and others has nicely confirmed
this.
Now, would we like to see simple peptide catalysts get incorporated into
simple protein structures, and for their function to thereby improve? Sure.
Would we like to see simple enzymes get together to take on more complex
tasks? You betcha. Do you for a moment believe that either of these is
full-stop outside the realm of realistic probabilities? Sure you do, what
am I thinking (slaps head)! OK, look, set some realistic guidelines,
including, say kcat's or Km's or number / type of chemical transformations
or whatnot; I'll come back and slap your guidelines around a bit, but I'm
sure we can come to an agreement that will allow you to be proved wrong
within a few years, if not immediately. Tell you what, we can even expand
your Universe to include nucleic as well as amino acids, that should allow
us to probe even more realistic origins scenarios.
See, this is how science is done. Hypothesis. Experiment. Ass-kicking.
Take floppy there back to the field for the crows to chew on; he's done.
Non-woof
Tracy Hamilton
"Deaddog" <elling...@yahoo.com> wrote in message
news:bqlrvp$os5$1...@geraldo.cc.utexas.edu...
[snip]
> On the other hand, many people would claim that simple enzymatic functions
> that could support relatively limited metabolisms evolved at one point,
and
> that more complex function arose from duplication and diversification of
> these simple functions. There is an abundance of evidence to support this
> non-strawman theory of enzyme function and metabolic origins. For
example,
> simple peptides are more than capable of acting as catalysts. A former
> advisor used to chortle that lysine is a kick-ass oxaloacetate
> decarboxylase, and it is.
<ID mode>
Lysine is an irreducibly complex peptide (remove just one amino
acid and it loses all function), therefore it is unlikely to have evolved.
If you don't think it is complex, give me its exact wavefunction,
putrescent pup!
</ID mode>
[snip]
Tracy P. Hamilton
r norman
Sorry, but if you want to go into snarky mode, you have to be
punctiliously correct. Lysine is an amino acid, not a peptide. Your
point is still valid -- it is "irreducibly complex". Complex, as you
say, by trying to compute its wavefunction. Irreducible because
removing any single atom from it makes it into something else
entirely. The only way lysine could be produced is "all of a piece",
not from any smaller precursors, according to ID mode thinking.
AR
Sean Pitman wrote:
> >You are
> > merely presuming your conclusion when you say that "no such mindless
> > process can give rise to a greater level of complexity... that goes
> > very far beyond what its original programming allowed it to do".
>
> This conclusion happens to be my hypothesis. That is what the
> scientific method is all about. You observe a given phenomenon and
> then make a conclusion/hypothesis to explain this phenomenon. This is
> a valid scientific process as long as the hypothesis makes a testable
> prediction that can in fact be disproved or "falsified". This is what
> I have done.
Pitman does not understand the scientific process. He has the components
of the process confused, and blended together into a mish mash.
I've pointed this out to him before. And he has always been unwilling
to discuss his mistaken notions about the scientific process.
Gee, isn't that a surprise.
His confusion is one reason why he has a tendency to present many of
his components of the scientific process as pairs of what are actually
separate ideas, e.g., "conclusion/hypothesis". These of course do not have
the same meanings in the scientific process.
He cannot produce the correct definition of a theory or a hypothesis
and he cannot explain the role or either in the scientific process.
Of course he is presuming his conclusion as part of his
"prediction/hypothesis/theory/lunch/dinner/scientific test/...
He has little or no idea of how the scientific process works
or what the terms mean.
Regards
Sean Pitman
> news:80d0c26f.03120...@posting.google.com...:
> > I have predicted that no mindless process will ever be
> > able to create anything new within a given level of complexity or
> > beyond in real time. I have drawn this line at several thousand amino
> > acids working at the same time.
>
> Well, um, who gives a rat's ass? You can define it to be 'my big floppy
> friend the scarecrow' for all I care. A strawman is a strawman is a
> strawman. No one claims that complex enzymatic functions arose with great
> alacrity from long strings of random protein sequence information.
Talk about a strawman! I'm not even saying that complex enzymatic
functions need to arise from random protein sequences. I'm saying
that starting with something that already works evolution will not be
able to evolve anything else that works in a different way at the same
level of complexity or greater beyond the lowest levels of functional
complexity. In other words, if the starting point is at a level of
functional complexity that requires a few thousand amino acids working
together at the same time in a fairly specified sequential order, no
new types of function will evolve at that level or beyond.
This is no strawman. This is exactly what evolutionists claim that
evolution has done and is capable of doing. And yet, evolutionists
have failed to show how such novel functional evolution is remotely
possible. The neutral gaps involved are truly enormous and expand
exponentially with each additional minimum amino acid requirement.
How are the crossing of such gaps achieved via the mindless processes
of random mutation and natural selection regardless of the original
functional sequences that one starts with?
> This has
> of course been tested: Keefe and Szostak (2001), Nature 410:715 (the enzyme
> work has yet to appear, though). High-affinity binders similar to modern
> catalysts don't occur frequently (although if I read your argument
> correctly, you would have predicted not at all?).
Obviously you don't read my argument correctly. Such binding
affinities are not a problem at all since they require few amino acids
and little specificity. The minimum amino acid requirement is quite
small indeed. The level of functional complexity is therefore very
low indeed.
> Duh. These experiments
> are cool but not necessarily relevant to origins, and certainly not relevant
> to understanding modern protein evolution, which as we have previously
> stated and as you have previously ignored occurs in a wonderfully modular
> fashion that allows high order complexity to be achieved.
Again, you repeat these bold statements but give no evidence to
support yourself beyond the historical demonstration of similarities.
You have not even attempted to explain how the gaps between different
kinds of highly complex functions could have been crossed. You just
have this amazing faith that they were crossed via mindless
evolutionary processes alone based on weak historical observations
that there are certain similarities between various functional
systems. You and many other evolutionists fall into the same classic
error of thinking that similarities support the idea of common
evolutionary origin over the idea of common intelligent design.
Similarities support both positions equally well. The only way you
can rule out the idea that intelligence and only intelligence (at the
level of humans or beyond) could have given rise to such levels of
functional complexity is by showing that a mindless process can
actually approach something, anything, within such a level of
functional complexity. This is a falsifiable hypothesis, as
falsifiable as the idea that no cow can jump over my house, and yet
you evolutionists haven't even come close to falsifying this position.
Statistically, it is impossible this side of zillions of years. You
have not overcome this problem in an even remotely convincing way.
You set up your scarecrows, but have little else to offer.
> Similarly, your attempts to squish Hall's most excellent experiments on the
> evolutionary potential of cryptic sequences into some sort of diatribe on
> design are just ... weird.
How so? What Hall did clearly shows the limits of evolutionary
processes. His experiments clearly show that the ratio of certain
functions in sequence space is quite low indeed and that they get
exponentially lower at higher and higher levels of functional
complexity (i.e., more and more amino acids required at minimum).
How is this idea "weird"?
> If you want to tilt at windmills, at least have
> the good sense to trade in your wheelbarrow for a horse, your pixie stick
> for a lance, and your intellect for ... well, we shouldn't move outside the
> realm of possibility.
Nice verbiage . . . but what the heck does it mean? What do you have
as evidence against my position, predictions, and hypothesis besides
meaningless statements like this?
> On the other hand, many people would claim that simple enzymatic functions
> that could support relatively limited metabolisms evolved at one point, and
> that more complex function arose from duplication and diversification of
> these simple functions. There is an abundance of evidence to support this
> non-strawman theory of enzyme function and metabolic origins. For example,
> simple peptides are more than capable of acting as catalysts.
Yes, like the lactase and nylonase enzymes, which requires no more
than 480 or so amino acids in a fairly flexible order at minimum.
Nothing much higher than this level of complexity has ever been shown
to evolve. Evolution simply stalls out at this rather low end of the
spectrum of functional complexity. What else do you have?
> A former
> advisor used to chortle that lysine is a kick-ass oxaloacetate
> decarboxylase, and it is. And the formation of protein structure, the
> precursor to common catalytic function, is also surprisingly easy. I think
> one of the best papers in this regard is Kamtekar et al. (1993), Science
> 262:1680.
How many amino acids at minimum were required? That is the question.
What do you have in regards to this question.
> Basically, even very simple codes based on very simple
> physicochemical models can lead to the formation of coherent protein
> structures. Follow-up work by the Hecht lab and others has nicely confirmed
> this.
How many amino acids required at minimum for the beneficial functions
of these protein sequences?
> Now, would we like to see simple peptide catalysts get incorporated into
> simple protein structures, and for their function to thereby improve?
Actually, this does happen, but the individual functions, the protein
domains, do not improve above the level of functional complexity
requiring a few hundred amino acids working together at the same time.
> Sure.
> Would we like to see simple enzymes get together to take on more complex
> tasks? You betcha.
Oh, I bet you would, but it just doesn't happen now does it?
> Do you for a moment believe that either of these is
> full-stop outside the realm of realistic probabilities? Sure you do, what
> am I thinking (slaps head)!
Keep slapping that head of yours until you find some realistic
explanation or an actual example that proves me wrong.
> OK, look, set some realistic guidelines,
> including, say kcat's or Km's or number / type of chemical transformations
> or whatnot; I'll come back and slap your guidelines around a bit, but I'm
> sure we can come to an agreement that will allow you to be proved wrong
> within a few years, if not immediately.
I have set guidelines. The guidelines that I have set require
functions will minimal amino acid requirements of a few thousand amino
acids working together at the same time in a fairly specified order to
be evolved. Such levels of complexity are very common in all living
things. For example, all bacterial motility systems require several
thousand rather specified amino acids, in the form of several
different proteins, working together at the same time for the function
of motility to be realized in a beneficial way. If you can show any
new function evolving within such a level of functional complexity,
you will have something. Until then, you have nothing but a scarecrow
theory.
> Tell you what, we can even expand
> your Universe to include nucleic as well as amino acids, that should allow
> us to probe even more realistic origins scenarios.
Fine. Amino acid sequences are coded for by nucleotide sequences by a
minimum ratio of 3:1. For each additional amino acid requirement, the
sequence space also increases by a factor of 3. However, the
beneficial nucleotide sequences in sequence space do no increase by a
factor of three at each successive increase in functional complexity.
That is your problem either way you look at it. Each step up the
ladder of complexity (minimum amino acid or nucleic acid requirement)
results in an exponential increase in the size of sequence space
relative to the number of beneficial sequences contained by that
space. Like rapidly separating stepping-stones, these beneficial
sequences are soon so far apart on average that trillions upon
trillions of years of random walk simply are not enough to cross
through all the non-beneficial sequences that separate the beneficial
sequences in sequence space. The problem here is that natural
selection can select, in a positive way, only those sequences that
have some sort of beneficial function. If beneficial sequences are
very far apart in sequence space, requiring more and more mutations to
reach, the random walk involved gets exponentially longer with each
additional step that is required before a new type of beneficial
function is realized.
> See, this is how science is done. Hypothesis. Experiment. Ass-kicking.
Exactly. You have your hypothesis, but no experimental support. So,
for now, it is your ass with the boot in it.
> Take floppy there back to the field for the crows to chew on; he's done.
That's for sure! Your floppy theory of evolution has little left for
those with half a mind to understand the statistical problems with the
theory. Only those who are devoted to it as "more than a theory" have
the religious fortitude to stick by such an ailing theory.
> Non-woof
Woof
Deaddog
"AR" <xy...@pitt.edu> wrote in message news:3FCF6409...@pitt.edu...:
> Pitman does not understand the scientific process. He has the components
> of the process confused, and blended together into a mish mash.
> I've pointed this out to him before. And he has always been unwilling
> to discuss his mistaken notions about the scientific process.
This explanation certainly makes much of the gibberish that passes as a
reply easier to deal with, if not understand.
> He cannot produce the correct definition of a theory or a hypothesis
> and he cannot explain the role or either in the scientific process.
Right, then we should do the job for him:
So, Sean, if we take some thousand or more amino acids that have never
worked together before and show that they can now evolve to work together in
a functional way, that would satisfy your 'test,' correct?
And, to avoid an avalanche of "Pay me $150 you lying weasel" strings, please
specify exactly what you mean so that it can be independently verified
whether or not it has already been demonstrated by science. I think my
definition, above, is pretty nifty: we find some set of proteins (whose sum
is > 1000 amino acids) and that have never worked together before in
biology, and show that by using evolution they can now work together to form
a functional pathway. Isn't that really what you're trying to get at?
Otherwise, well, so far all you've written is a bunch of gibberish that
cannot in any way, shape, or form be reduced to a question, hypothesis,
theory, or even a decent stain under a coasterless glass of lemonade.
Non-woof
howard hershey
Sean Pitman wrote:
> "Deaddog" <elling...@yahoo.com> wrote in message news:<bqlrvp$os5$1...@geraldo.cc.utexas.edu>...
>
>>"Sean Pitman" <seanpi...@naturalselection.0catch.com> wrote in message
>>news:80d0c26f.03120...@posting.google.com...:
>
>
>>>I have predicted that no mindless process will ever be
>>>able to create anything new within a given level of complexity or
>>>beyond in real time. I have drawn this line at several thousand amino
>>>acids working at the same time.
>>
>>Well, um, who gives a rat's ass? You can define it to be 'my big floppy
>>friend the scarecrow' for all I care. A strawman is a strawman is a
>>strawman. No one claims that complex enzymatic functions arose with great
>>alacrity from long strings of random protein sequence information.
>
>
> Talk about a strawman! I'm not even saying that complex enzymatic
> functions need to arise from random protein sequences.
When you say that in order for a new function to arise you must change
"a few thousand amino acids" you are indeed saying that "complex
enzymatic functions need to arise from random protein sequences". At
least to the extent that you are saying anything.
You are *specifically* denying, for example, that a single mutation can
lead two proteins that previously did not interact to interact. You are
*specifically* denying that a single mutation can lead two proteins that
currently interact to interact in a different fashion, perhaps with a
modified function. You are *specifically* claiming that the only way to
generate a two-protein complex that performs a new function is to start
from scratch and go through "several thousand amino acid" changes.
Otherwise, there is no difference between your "lowest levels of
functional complexity" and "higher levels of functional complexity".
You agree that single mutations can alter function at low levels of
functional complexity. What prevents it from happening at high levels?
You claim it is because at high levels, unlike at lower levels, you
need thousands of amino acid changes.
In short, you avoid the strawman "number of amino acids" argument when
you discuss antibiotic resistance and similar systems only to re-invent
it when the system is at a "higher level of complexity". You NEVER
justify your reasoning for this sudden rapid change in number of events
needed to effect functional change.
> I'm saying
> that starting with something that already works evolution will not be
> able to evolve anything else that works in a different way at the same
> level of complexity or greater beyond the lowest levels of functional
> complexity. In other words, if the starting point is at a level of
> functional complexity that requires a few thousand amino acids working
> together at the same time in a fairly specified sequential order, no
> new types of function will evolve at that level or beyond.
I did mention reversion of any of several mutations of bacterial
flagella which produce immotile flagella which still retain protein
export abilities, did I not (although the forward mutation would work as
well)? You agree that bacterial flagella are multiprotein complex
systems involving thousands of amino acids, right? You agree that it
has a motility function, right? Some bacterial fagella also have a
protein export capability, right? You would agree that single mutations
can produce a complex, multiprotein system that only have the second
function. Would you then agree that reversion (also a single mutation)
can produce a new function (motility) from the system with only protein
export utility?
>
> This is no strawman. This is exactly what evolutionists claim that
> evolution has done and is capable of doing.
No it isn't. What scientists propose does not involve thousands of
selectively neutral changes that must all occur (in order?) in order to
produce a selectable effect. It involves duplications and divergence
involving a *few* or even *one* change. It involves changes that allow
multifunctionality for individual proteins (also single or a few
changes). In NO case do molecular evolutionary biologists propose
starting with some quasi-random sequence and randomly walking through
selectively neutral space for thousands of changes in amino acids until
the one keystone change magically produces the only possible selectable
change. Now proteins may indeed undergo thousands of selectively
neutral changes, but these changes are typically selectively irrelevant
in that it doesn't matter whether any or all or an entirely different
set of changes occurred. All that matters is the one or few mutations
of selective relevance.
> And yet, evolutionists
> have failed to show how such novel functional evolution is remotely
> possible. The neutral gaps involved are truly enormous and expand
> exponentially with each additional minimum amino acid requirement.
> How are the crossing of such gaps achieved via the mindless processes
> of random mutation and natural selection regardless of the original
> functional sequences that one starts with?
Because there are no such enormous neutral gaps that *must* be crossed.
You are positing a problem that could only have meaning if you started
with a protein which was essentially (relative to the end protein) a
random sequence with no similarity or active sites with related function
to the end result. Evolutionary biologists *specifically*, by pointing
out the likely precursor proteins, which *always* have sequence
similarity (especially in the functional active sites), disagree that
evolution happens by the strawman "thousands of changes" model you present.
>>This has
>>of course been tested: Keefe and Szostak (2001), Nature 410:715 (the enzyme
>>work has yet to appear, though). High-affinity binders similar to modern
>>catalysts don't occur frequently (although if I read your argument
>>correctly, you would have predicted not at all?).
>
>
> Obviously you don't read my argument correctly. Such binding
> affinities are not a problem at all since they require few amino acids
> and little specificity. The minimum amino acid requirement is quite
> small indeed. The level of functional complexity is therefore very
> low indeed.
Then where do you think the "thousands of amino acid" changes come in?
>>Duh. These experiments
>>are cool but not necessarily relevant to origins, and certainly not relevant
>>to understanding modern protein evolution, which as we have previously
>>stated and as you have previously ignored occurs in a wonderfully modular
>>fashion that allows high order complexity to be achieved.
>
>
> Again, you repeat these bold statements but give no evidence to
> support yourself beyond the historical demonstration of similarities.
> You have not even attempted to explain how the gaps between different
> kinds of highly complex functions could have been crossed.
How big a gap exists between the alpha globin of hemoglobin and the beta
globins of hemoglobin? Why is it impossible to produce the latter by
duplication and divergence from the former, with the irreducible
complexity of hemoglobins in organisms with both being an emergent
property? Where are the "enormous neutral gaps" that prevent the
formation of a 'system' that involves these two proteins interacting
with each other at the same time and place to produce a function?
> You just
> have this amazing faith that they were crossed via mindless
> evolutionary processes alone based on weak historical observations
> that there are certain similarities between various functional
> systems.
The similarities show which small sections of proteins are crucial to
function and which parts are irrelevant to function. It also shows
which parts had to change to change function. These are often small and
require only a few changes.
> You and many other evolutionists fall into the same classic
> error of thinking that similarities support the idea of common
> evolutionary origin over the idea of common intelligent design.
> Similarities support both positions equally well.
Only if the designer chose to produce the type of nested hierarchy that
is also produced by history rather than the type of changes that human
designers would make (involving extensive borrowing and changes only in
the functionally relevant rather than the functionally irrelevant parts
to acheive local adaptive features). But since the designer is your
HYPE (hypothetical posited entity), you can design him/her/it/they any
way you want to do anything you want him/her/it/them to do.
> The only way you
> can rule out the idea that intelligence and only intelligence (at the
> level of humans or beyond) could have given rise to such levels of
> functional complexity is by showing that a mindless process can
> actually approach something, anything, within such a level of
> functional complexity.
And this "level of functional complexity", at its minimum, must be
what....? Two proteins interacting? Three? Proteins that total 600
amino acids? 1200? Do they have to have 20 amino acid sites that
*must* change from some hypothetical precursor protein? 200? 2000?
You never do get around to actually telling us what you mean by "level
of complexity" and how we would recognize it, do you? All you do is say
that for things like antibiotic resistance the complexity is low,
involving as little as a single amino acid change, but for things that
involve 2?, 3? proteins working together, it involves "thousands of
amino acids". Is that "thousands of amino acids" that must change to
reach a new function or just "thousands of amino acids" in the protein?
You never say. Evasion. Evasion. Evasion. [Or, to be kind,
unclarity of thought.]
> This is a falsifiable hypothesis, as
> falsifiable as the idea that no cow can jump over my house, and yet
> you evolutionists haven't even come close to falsifying this position.
> Statistically, it is impossible this side of zillions of years. You
> have not overcome this problem in an even remotely convincing way.
> You set up your scarecrows, but have little else to offer.
Yet you never explicitly say what step cannot be accomplished. All you
say is that it is the step involving "thousands of amino acids" or
"enormous neutral gaps" or some other word salad.
>>Similarly, your attempts to squish Hall's most excellent experiments on the
>>evolutionary potential of cryptic sequences into some sort of diatribe on
>>design are just ... weird.
>
>
> How so? What Hall did clearly shows the limits of evolutionary
> processes. His experiments clearly show that the ratio of certain
> functions in sequence space is quite low indeed and that they get
> exponentially lower at higher and higher levels of functional
> complexity (i.e., more and more amino acids required at minimum).
> How is this idea "weird"?
It is weird because you seem to think that evolution is 'magic' just
like your preferred mechanism (an intelligent something swoops down and
poofs whatever is needed into existence from nothing at all). Evolution
does not claim that one can generate any activity from any random
sequence in five years by the application of a little selective
pressure. It never did. Evolution works by "descent with modification"
not "magic thousands of changes". It always has to start with something
which can reasonably be modified to a new or useful function.
>>If you want to tilt at windmills, at least have
>>the good sense to trade in your wheelbarrow for a horse, your pixie stick
>>for a lance, and your intellect for ... well, we shouldn't move outside the
>>realm of possibility.
>
>
> Nice verbiage . . . but what the heck does it mean? What do you have
> as evidence against my position, predictions, and hypothesis besides
> meaningless statements like this?
Your position is a tilting against a windmill (or a strawman). Your
argument is simply irrelevant.
>>On the other hand, many people would claim that simple enzymatic functions
>>that could support relatively limited metabolisms evolved at one point, and
>>that more complex function arose from duplication and diversification of
>>these simple functions. There is an abundance of evidence to support this
>>non-strawman theory of enzyme function and metabolic origins. For example,
>>simple peptides are more than capable of acting as catalysts.
>
>
> Yes, like the lactase and nylonase enzymes, which requires no more
> than 480 or so amino acids in a fairly flexible order at minimum.
The number of amino acids is irrelevant. The number of mutational
changes needed to reach a selectable function is not. Can you present a
clear argument wrt why you think the total number of amino acids is
relevant and not simply a number presented in order to generate a
strawman argument?
> Nothing much higher than this level of complexity has ever been shown
> to evolve. Evolution simply stalls out at this rather low end of the
> spectrum of functional complexity. What else do you have?
>
>
>>A former
>>advisor used to chortle that lysine is a kick-ass oxaloacetate
>>decarboxylase, and it is. And the formation of protein structure, the
>>precursor to common catalytic function, is also surprisingly easy. I think
>>one of the best papers in this regard is Kamtekar et al. (1993), Science
>>262:1680.
>
>
> How many amino acids at minimum were required? That is the question.
> What do you have in regards to this question.
Why do you think that the number of amino acids in a protein(s) is
relevant to evolution of new functionality? Other, of course, than that
the number is important in a strawman argument that implies that new
functions arise from random starting sequences.
>>Basically, even very simple codes based on very simple
>>physicochemical models can lead to the formation of coherent protein
>>structures. Follow-up work by the Hecht lab and others has nicely confirmed
>>this.
>
>
> How many amino acids required at minimum for the beneficial functions
> of these protein sequences?
Why do you think that the number of amino acids in a protein(s) is
relevant to evolution of new functionality? Other, of course, than that
the number is important in a strawman argument that implies that new
functions arise from random starting sequences.
>>Now, would we like to see simple peptide catalysts get incorporated into
>>simple protein structures, and for their function to thereby improve?
>
>
> Actually, this does happen, but the individual functions, the protein
> domains, do not improve above the level of functional complexity
> requiring a few hundred amino acids working together at the same time.
Why do you think that the number of amino acids in a protein domain is
relevant to evolution of new functionality? Other, of course, than that
the number is important in a strawman argument that implies that new
functions arise from random starting sequences.
>> Sure.
>>Would we like to see simple enzymes get together to take on more complex
>>tasks? You betcha.
>
>
> Oh, I bet you would, but it just doesn't happen now does it?
>
>
>>Do you for a moment believe that either of these is
>>full-stop outside the realm of realistic probabilities? Sure you do, what
>>am I thinking (slaps head)!
>
>
> Keep slapping that head of yours until you find some realistic
> explanation or an actual example that proves me wrong.
>
>
>> OK, look, set some realistic guidelines,
>>including, say kcat's or Km's or number / type of chemical transformations
>>or whatnot; I'll come back and slap your guidelines around a bit, but I'm
>>sure we can come to an agreement that will allow you to be proved wrong
>>within a few years, if not immediately.
>
>
> I have set guidelines. The guidelines that I have set require
> functions will minimal amino acid requirements of a few thousand amino
> acids working together at the same time in a fairly specified order to
> be evolved.
There are proteins or heterodimers or larger complexes that are several
thousand amino acids long, but I know of none that *require* several
thousand *specific* (or invariant) amino acids for function. Do you?
All the ones I know of are much more flexible wrt sequence than that.
Perhaps the five histones that make up the nucleosome comes closest, but
histones are pretty small (about 740 amino acids adding up all five) and
I doubt that most of the amino acids are absolutely specified (even
though histones have about the most strongly conserved sequences in all
eucaryotes)? Indeed, Michael Behe claimed that one (count 'em, one)
amino acid was always invariant in one of the histones -- I forget which
one -- (but in the same year, 1990, but after he published, several
species of ciliate were found to have a variant amino acid at that
site). Of course, the change was a conservative change, but it was a
change. In all other proteins the number of "invariant" amino acids and
conserved (functionaly relevant) sequence is much smaller.
> Such levels of complexity are very common in all living
> things. For example, all bacterial motility systems require several
> thousand rather specified amino acids, in the form of several
> different proteins, working together at the same time for the function
> of motility to be realized in a beneficial way.
But that does not mean that one has to change several thousand amino
acids in order to generate a bacterial 'mobility' system. One can, as I
point out, change a specific single amino acid and convert a "protein
export" system into a system which is both a "protein export" and a
"mobility" system. Now, admittedly this is a simple reversion so that
the "protein export" system was, in the historical past, a system with a
different function. But as evidence that one does not need "thousands
of amino acid" changes to generate new or altered function, regardless
of how many amino acids or proteins are in the system, I think it makes
its point: The amount of change needed to alter function is not related
to the complexity of the system.
> If you can show any
> new function evolving within such a level of functional complexity,
> you will have something. Until then, you have nothing but a scarecrow
> theory.
If you can present me with a system that could not, by any known
mechanism, including duplication and divergence and chimeric duplication
have evolved into a current without changing "thousands of amino acids",
you would be able to convince me. Until you can present such a system
that requires "thousands of amino acids" to change (i.e., the equivalent
of making new proteins from random sequences), I will regard that as the
classic creationist strawman misunderstanding of how these systems evolve.
>>Tell you what, we can even expand
>>your Universe to include nucleic as well as amino acids, that should allow
>>us to probe even more realistic origins scenarios.
>
>
> Fine. Amino acid sequences are coded for by nucleotide sequences by a
> minimum ratio of 3:1. For each additional amino acid requirement, the
> sequence space also increases by a factor of 3. However, the
> beneficial nucleotide sequences in sequence space do no increase by a
> factor of three at each successive increase in functional complexity.
> That is your problem either way you look at it. Each step up the
> ladder of complexity (minimum amino acid or nucleic acid requirement)
> results in an exponential increase in the size of sequence space
> relative to the number of beneficial sequences contained by that
> space. Like rapidly separating stepping-stones, these beneficial
> sequences are soon so far apart on average that trillions upon
> trillions of years of random walk simply are not enough to cross
> through all the non-beneficial sequences that separate the beneficial
> sequences in sequence space. The problem here is that natural
> selection can select, in a positive way, only those sequences that
> have some sort of beneficial function. If beneficial sequences are
> very far apart in sequence space, requiring more and more mutations to
> reach, the random walk involved gets exponentially longer with each
> additional step that is required before a new type of beneficial
> function is realized.
And positing that beneficial sequences are far apart in sequence space,
requiring more and more mutations to reach does not make it true nor
does it make it the way evolution works (which is by modification of
pre-existing sequences that have function).
>>See, this is how science is done. Hypothesis. Experiment. Ass-kicking.
>
>
> Exactly. You have your hypothesis, but no experimental support. So,
> for now, it is your ass with the boot in it.
Why should I present evidence *for* what I regard as an irrelevant
strawman model of evolution?
>>Take floppy there back to the field for the crows to chew on; he's done.
>
>
> That's for sure! Your floppy theory of evolution has little left for
> those with half a mind to understand the statistical problems with the
> theory. Only those who are devoted to it as "more than a theory" have
> the religious fortitude to stick by such an ailing theory.
I agree that your understanding of statistical problems took half a
mind. I would suggest the lower half.
>
>
>>Non-woof
>
>
> Woof
>
> Sean
> www.naturalselection.0catch.com
>
Mark Isaak
seanpi...@naturalselection.0catch.com (Sean Pitman) wrote:
>Talk about a strawman! I'm not even saying that complex enzymatic
>functions need to arise from random protein sequences. I'm saying
>that starting with something that already works evolution will not be
>able to evolve anything else that works in a different way at the same
>level of complexity or greater beyond the lowest levels of functional
>complexity. In other words, if the starting point is at a level of
>functional complexity that requires a few thousand amino acids working
>together at the same time in a fairly specified sequential order, no
>new types of function will evolve at that level or beyond.
If I understand you correctly, you are saying that it is impossible
for evolution to produce a new functional gene without eliminating at
least one other gene. Is that what you are saying?
--
Mark Isaak at...@earthlink.net
"Voice or no voice, the people can always be brought to the bidding of
the leaders. That is easy. All you have to do is tell them they are
being attacked, and denounce the pacifists for lack of patriotism and
exposing the country to danger." -- Hermann Goering
sweetnes...@yahoo.com
Talk about someone who runs away from evidence, just to post the same,
already disproved nonsense all over again.
>I'm saying that starting with something that
>already works evolution will not be able to
>evolve anything else that works in a different
>way at the same level of complexity or greater
>beyond the lowest levels of functional complexity.
Yes, we know. And it has been explained to you why you are wrong. Just
minutes ago, I did it in your "Mindless Creativity" thread. A few days
ago I did it in the thread on your theory.
>And yet, evolutionists have failed to show how
>such novel functional evolution is remotely possible.
Failed to do the impossivble and force a process that happens over
millenia to happen in the lab within a century.
>The neutral gaps involved are truly enormous and
>expand exponentially with each additional minimum
>amino acid requirement.
Not true. And minimum amino acid requirement is something you
invented.
See the above referenced threads for detailed refutation.
>How are the crossing of such gaps achieved via the
>mindless processes of random mutation and natural
>selection regardless of the original functional
>sequences that one starts with?
I have explained it to you. More then once.
>Such binding affinities are not a problem at
>all since they require few amino acids and
>little specificity. The minimum amino acid
>requirement is quite small indeed. The level
>of functional complexity is therefore very
>low indeed.
And from such small changes, large changes follow.
>Again, you repeat these bold statements but
>give no evidence to support yourself beyond
>the historical demonstration of similarities.
We are observing the processes currently. All that is required is that
those same processes happened in the past. If you have proof that the
laws of the universe were different, and then changed in the last few
centuries, please say so, and provide the evidence.
>You have not even attempted to explain how the gaps
>between different kinds of highly complex functions
>could have been crossed.
Yes we did. I did it myself, in quite a bit of detail, in this
newsgroup.
>You and many other evolutionists fall into the same
>classic error of thinking that similarities support
>the idea of common evolutionary origin over the idea
>of common intelligent design.
Because of its superiority. I'm never sure which of my messages will
make it to the newsgroup first, so I'll quote the last section of my
answer to your "Mindless Creativity" thread (which is, as all other
your threads are, just another repetition):
<start quote>
No faith is needed for evolution. But evolution applies from the first
roughly functioning cell onwards; you might be talking about
abiogenesis, so let's analyze that for a moment. How did the first
cell come about?
This is something that is quite unknown, and entirely theoretical. So,
yes, unlike the case of evolution, one cannot make one's mind based
entirely on evidence. What do we do?
You might propose that, since we don't know, it is equally rational to
simply say that there was an Intelligent Designer who designed the
first cell, as it is to assume that the mindless processes did it. You
might say that it takes faith in both cases, so there is no real
difference.
If you did so (and I don't know if you would, but I have a general
idea), you would be wrong. There is a simple reason to assume that the
first cell arose by mindless processes rather then by intelligent
design. The reason is evidence of existence.
We *know*, without doubt, that mindless processes exist. Everything
that happens, happens according to the laws of the universe. We have
ascertained without much doubt that the same laws (without any large,
visible changes) applied for quite a few billions of years. We know
that those laws were around when the life first began. Therefore, we
have good reason to think that the laws of the universe were involved
in the begining of life.
As for Intelligent Designer...we have no idea if a supernatural entity
such as he exists or not. We see no evidence of his existence, in the
present or in the past. He is entirely in the domain of imagination,
and as such we can imagine anything about him, and therefore measure
nothing. Not only have we no reason to assume his existence, but
taking him as an "option" would literally mean end of any further
research - for if can you learn anything about an invisible,
intanglible being that never does anything, how can you learn anything
about its works?
How did a star form? If we assume it formed by mindless processes, we
can use our knowledge of the laws of physics, and see if we can
discover a solution. After many years of work, we may produce a
theory, compare it to the reality, and see if it stands up to
scrutiny. If we assume that a Designer made it, that is it. We give
up, and say "goddidit", the end. We cannot know anything further.
Through most of the Dark Ages, people took the second approach;
whatever it is, God made it to be that way. This is, in fact, the
reason why that period of time is called "The Dark Ages". Modern
science uses the first approach, and it got as quite a bit further.
So, in case of abiogenesis, I will look at both options: accept a
Designer without *any* reason to do so, plop on a chair, and say
"done". Or assume that the processes that did EVERYTHING ELSE around
me also produced life, and try to figure out how they did it.
Mindless processes, Intelligent Designer, whichever it is, gave us
free will to make our own choices. Each to their own, as they say.
<end quote>
So, even if we ignore the facts (as you do), and claim that there is
no reason to favor one side over the other, there is this reason
above. It is a very good reason, IMO.
>Statistically, it is impossible this side of zillions of years.
Untrue, see referenced posts.
>You have not overcome this problem in an even remotely
>convincing way.
It is impossible to convince someone who refuses to look at the
evidence.
>You set up your scarecrows, but have little else to offer.
Hundreds of thousands of professional scientists do so. Interesting.
>How so? What Hall did clearly shows the limits of evolutionary
>processes. His experiments clearly show that the ratio of certain
>functions in sequence space is quite low indeed and that they get
>exponentially lower at higher and higher levels of functional
>complexity (i.e., more and more amino acids required at minimum).
>How is this idea "weird"?
Because he did nothing of the kind. He showed how functions can
quickly adapt to new conditions, and that a function can arise from a
different one. He also showed that, as expected, evolution works very
slow when there is no basis from which a particular function can
quickly evolve. There was nothing in his findings that contradicted
evolutionary theory in any way, shape or form.
Again, see my answer to you in "Mindless Creativity" thread. To avoid
repetition, I will refer to the previous sentence as "Statement A".
>Yes, like the lactase and nylonase enzymes, which
>requires no more than 480 or so amino acids in a
>fairly flexible order at minimum.
Bull. Statement A.
>Nothing much higher than this level of complexity
>has ever been shown to evolve. Evolution simply
>stalls out at this rather low end of the spectrum
>of functional complexity. What else do you have?
Statement A.
>How many amino acids at minimum were required?
>That is the question.
For which function? There are many functions where one will suffice.
Two, three, five, ten, fifteen...there are examples of all sorts of
short polypeptides performing various functions.
And, again, Statement A.
>What do you have in regards to this question.
Statement A. Plus all the things mentioned in the post within "Sean
Pitman's Theory" thread. Plus about ten-thousandfold as much evidence
in molecular evolution papers published in last fourty years.
>How many amino acids required at minimum for the
>beneficial functions of these protein sequences?
The number of amino acids does not matter. Statement A.
>Actually, this does happen, but the individual functions,
>the protein domains, do not improve above the level of
>functional complexity requiring a few hundred amino acids
>working together at the same time.
But they recombine. They adapt and optimize without "searching"
through every possible combination of residues. Proteines also change
functions, or can be pushed from one function to another by selective
pressures (see the example I gave in the first post in "Sean Pitman's
Theory" thread). Statement A - also some additional details.
>Oh, I bet you would, but it just doesn't happen now does it?
I gave you examples of that happening. Observed. In lab.
>Keep slapping that head of yours until you find
>some realistic explanation or an actual example
>that proves me wrong.
I gave you examples. You ran away, waited for a week, then started
several new threads as if I said nothing.
>I have set guidelines. The guidelines that I have
>set require functions will minimal amino acid
>requirements of a few thousand amino acids working
>together at the same time in a fairly specified order
>to be evolved.
Considering how often we see developments of new, specific enzymes
(quite often), how often we see enzymes that used to work separately
now pairing together to do something else (occasionaly), and how often
we see entire existing system co-opted to perform novel functions
(rarely), it is statistically quite impossible that such a system you
describe won't develop in lab given just a few thousand years of
evolution. Also, Statement A.
>For example, all bacterial motility systems require
>several thousand rather specified amino acids, in
>the form of several different proteins, working
>together at the same time for the function of motility
>to be realized in a beneficial way.
Already covered.
>Until then, you have nothing but a scarecrow theory.
The theory fits all the relevant data, and can be used to make
exceedingly precise predictions. Do you have a theory that will fit
the data better and/or allows for better predictions?
>Fine. Amino acid sequences are coded for by nucleotide
>sequences by a minimum ratio of 3:1. For each additional
>amino acid requirement, the sequence space also increases
>by a factor of 3.
No, it does not. Run "genetic code degeneracy" through a search engine
for explanation why. I give up on getting you to open a book in
biochemistry (and I now utterly disbelieve that you ever took it with
any degree of success; if you passed biochemistry, and you can state
something like this above, your professor should resign immediately).
>The problem here is
...that nothing of what you say has anything to do with reality.
Statement A, plus the referenced thread on your theory.
>Exactly. You have your hypothesis, but no experimental
>support. So, for now, it is your ass with the boot in it.
Tons of experimental support. Plus confirmations from other branches
of science (geology, physics...). But I get tired. Tell me, where is a
singe bit of proof for ID theory? I mean, even if evolution was all
wrong, bogus, product of masonic conspiracy and whatnot, why would I
believe your half-assed bullshit about "Intelligent Designers", rather
then just say "I don't know"?
>Your floppy theory of evolution has little left for
>those with half a mind to understand the statistical
>problems with the theory.
Indeed, the world is fortunate to have people with half a mind, such
as yourself, who can show us all The Truth of Creation. Should I bow
before your magnificence?
Hm. Nah. I'll see what you have to say to the Statement A, and to the
evidence I gave in the "Sean Pitman's Theory" thread (which I should
have named Statement B at the beginning, and save myself quite a bit
of typing).
M.
MEC
Dear Expired Canine
I have been following this discussion. Sort of. And I was wondering
would Bcr/Abl or Ret/PTC chimeric proteins qualify as an example to
the good Dr. Pitman? Both are the results of recombination (chromosome
translocation) and both result in the induction of novel signaling
pathways, among other novel functions. Both fusion genes cause cancer
in humans (chronic myeloid leukemia in the case of Bcr/Abl and
medullary thyroid carcinoma for Ret/PTC). Bcr/Abl is >1500 aa long,
Ret/PTC is > than 1200 aa, depending on isotype of Ret.
Wot you think?
Deaddog
"MEC" <unre...@hotmail.com> wrote in message
news:c240c53.03120...@posting.google.com...
I think that anything that you reveal to be truth in advance of Pitman
agreeing to some set of rules is amazingly not going to be what he means.
Indeed, it seems from the other posters who have commented that this is far
from the first time someone has tried to just put things into a scientific
context for Pitman, only to be rebuffed by garbled, meandering statements
that could not be re-formulated as hypotheses even if one wanted to.
But it's a kick-ass example, and again shows how the evolution of novel
function via modular regulatory domains is quite possible.
Actually, it brings up the rather interesting question: is cancer good for
us, in an evolutionary sense? That is, an Intelligent Designer would
supposedly have tied down all those loose regulatory ends, flopping in the
evolutionary breeze, and thus would not have allowed us to get lumps the
size of pumpkins on our prostates or elsewhere. Ahem. However, this does
happen, because, well, evolution happens (in this case at the cellular
level). These Bad Things can be seen as a loss of organismal fitness, and
over time unsurprisingly result in the evolution of corresponding Good
Things to fix the Bad Things (think tumor suppressor genes).
Does the more complex network that results from selections for fitness
relative to oncogenesis (and other regulatory deficiencies) itself have
greater potential to evolve? Are things like our big ol' brains in part the
product of many years of evolving around regulatory deficiencies? "I
suffered from Lesch-Nyhan syndrome and all I got was this Broca's region!"
Nah. Too weird and speculative and stupid. For now.
Non-woof
Ian Musgrave & Peta O'Donohue
Address altered to avoid spam, delete RemoveInsert
On Fri, 5 Dec 2003 17:37:07 +0000 (UTC), unre...@hotmail.com (MEC)
wrote:
>"Deaddog" <elling...@yahoo.com> wrote in message news:<bqnvet$duf$1...@geraldo.cc.utexas.edu>...
[sean wrote in another post, not in this specific position in this
post
> > I have predicted that no mindless process will ever be
> > able to create anything new within a given level of complexity or
> > beyond in real time. I have drawn this line at several thousand amino
> > acids working at the same time.
just including it for orientation]
>> So, Sean, if we take some thousand or more amino acids that have never
>> worked together before and show that they can now evolve to work together in
>> a functional way, that would satisfy your 'test,' correct?
>>
>> And, to avoid an avalanche of "Pay me $150 you lying weasel" strings, please
>> specify exactly what you mean so that it can be independently verified
>> whether or not it has already been demonstrated by science. I think my
>> definition, above, is pretty nifty: we find some set of proteins (whose sum
>> is > 1000 amino acids) and that have never worked together before in
>> biology, and show that by using evolution they can now work together to form
>> a functional pathway. Isn't that really what you're trying to get at?
>>
>> Otherwise, well, so far all you've written is a bunch of gibberish that
>> cannot in any way, shape, or form be reduced to a question, hypothesis,
>> theory, or even a decent stain under a coasterless glass of lemonade.
>>
>> Non-woof
>
>
>Dear Expired Canine
>
>I have been following this discussion. Sort of. And I was wondering
>would Bcr/Abl or Ret/PTC chimeric proteins qualify as an example to
>the good Dr. Pitman? Both are the results of recombination (chromosome
>translocation) and both result in the induction of novel signaling
>pathways, among other novel functions. Both fusion genes cause cancer
>in humans (chronic myeloid leukemia in the case of Bcr/Abl and
>medullary thyroid carcinoma for Ret/PTC). Bcr/Abl is >1500 aa long,
>Ret/PTC is > than 1200 aa, depending on isotype of Ret.
You beat me to it. These examples are great as
1) A functional protein is created that does not previously exist, eg
BCR-ABL is a tyrosine kinase, and a nice one at that.
2) The proteins have interesting functional features not present in
the original proteins, BCR-ABL has different targeting and substrates
to ABL (we don't know what BCR does yet, it is probably not an enzyme)
3) They are definitely over 1000 amino acids (depending on isotype,
some fusions make short versions, eg there is a "mini" BCR-ABL that is
a mere 800 aa long).
4) They illustrate an important process in protein evolution. Not all
new proteins are generated by single amino acid substitutions, fusions
play a very important role (as does in-gene duplications), an example
is in a recent experiment where new, more efficient yeast hexose
transporters were generated by gene fusion (all done by mindless
processes, the experimenters just stuck the yeast in low hexose medium
and mutation (duplication-fusion) and natural selection did the rest).
Nonetheless, despite clear experimental evidence of generation of
functional enzymes (BCR-ABL tyrosine kinase) with clearly different
specificities (cytoplasmic rather than nuclear targeting) which are
larger than 1,000 aa long, I'm sure these will not be enough for Dr.
Pitman. The key is Dr' Pitman's statement:
"given level of complexity"
He will simply claim that BCR-ABL isn't complex enough. What it does
do is demolish his claim that "neutral gaps" get bigger as proteins
get larger.
When he says
> > I have drawn this line at several thousand amino
> > acids working at the same time.
It is not clear why. As a thought experiment, lets take a
"sufficiently complex" 1,800 aa protein, duplicate it, and fuse the
two together via their respective c-terminal and n-terminal domains,
you then have a very large, sufficiently complex protein working very
nicely (c-n terminal fusions happen all the time, in the lab and in
nature, without compromising the function of the proteins) well over
Dr. Pitman's limit. As another experiment, add a Green-fluorescent
protein domain to the C-terminal end of any large, complex but below
threshold protein, you will now have a large complex protein above Dr.
Pitman's limit that glows green as well.
The irony is that complex systems like the flagella, are not large
proteins, but non-cobvalent assemblies of lots of small-moderate sized
proteins, many of which are clear duplicates of others in the
assembly, so his whole "greater than 1,000 aa" argument does not apply
to them.
Cheers! Ian (posting rarely due to the arrival of Andrew Thomas)
=====================================================
Ian Musgrave Peta O'Donohue,Jack Francis and Michael James Musgrave
reyn...@werple.mira.net.au http://werple.mira.net.au/~reynella/
Southern Sky Watch http://www.abc.net.au/science/space/default.htm
Giant Sloth
As a lurker who admires your ID posts as at least sounding
intelligent, I'm wondering why you leave so many threads hanging, so
many arguments unrefuted in one place and then start a new thread
repeating the same apparently refuted arguments. Admittedly, you're
greatly outnumbered on TO, but could you at least pick one person to
respond to all their arguments? I would nominate
sweetnes...@yahoo.com since he's got unanswered arguments in two
threads and seems to have a good knowledge of the science involved.
He seems very willing to point out your apparent scientific errors.
Ideally, there should be a formal debate, I (and I assume others)
would pay close attention to that one.
RobinGoodfellow
> Actually, it brings up the rather interesting question: is cancer good for
> us, in an evolutionary sense? That is, an Intelligent Designer would
> supposedly have tied down all those loose regulatory ends, flopping in the
> evolutionary breeze, and thus would not have allowed us to get lumps the
> size of pumpkins on our prostates or elsewhere. Ahem. However, this does
> happen, because, well, evolution happens (in this case at the cellular
> level). These Bad Things can be seen as a loss of organismal fitness, and
> over time unsurprisingly result in the evolution of corresponding Good
> Things to fix the Bad Things (think tumor suppressor genes).
>
> Does the more complex network that results from selections for fitness
> relative to oncogenesis (and other regulatory deficiencies) itself have
> greater potential to evolve? Are things like our big ol' brains in part the
> product of many years of evolving around regulatory deficiencies? "I
> suffered from Lesch-Nyhan syndrome and all I got was this Broca's region!"
>
> Nah. Too weird and speculative and stupid. For now.
>
> Non-woof
Weird, yes. Speculative, maybe. Stupid - not necessarily. Check
out:
FW2.2: a quantitative trait locus key to the evolution of tomato fruit
size.
Frary A, Nesbitt, et. al.
Science. 2000 Jul 7;289(5476):85-8.
Quoth the abstract:
Domestication of many plants has correlated with dramatic increases in
fruit size. In tomato, one quantitative trait locus (QTL), fw2.2, was
responsible for a large step in this process .... The cause of the
QTL effect is a single gene, ORFX, that is expressed early in floral
development, controls carpel cell number, and has a sequence
suggesting structural similarity to the human oncogene c-H-ras p21.
OK, granted that a tomato growth spurt is not exactly the same thing
as swelling of brains to human proportions, but it would seem that
oncogenesis can play a positive role in the evolution of at least some
species. (Well, positive for us, anyway - I like my tomatoes big and
juicy.)
Sean Pitman
Sean Pitman
> > Talk about a strawman!
>
> Talk about someone who runs away from evidence, just to post the same,
> already disproved nonsense all over again.
Here is the link to my reply to most of this post in another thread
started by sweetnes (previous link posted wasn't correct):
Sarah Berel-Harrop
"Deaddog" <elling...@yahoo.com> wrote in message
news:bqqva6$cbh$1...@geraldo.cc.utexas.edu...
> Actually, it brings up the rather interesting question: is cancer good
for
> us, in an evolutionary sense? That is, an Intelligent Designer would
> supposedly have tied down all those loose regulatory ends, flopping in the
> evolutionary breeze, and thus would not have allowed us to get lumps the
> size of pumpkins on our prostates or elsewhere. Ahem. However, this does
> happen, because, well, evolution happens (in this case at the cellular
> level). These Bad Things can be seen as a loss of organismal fitness, and
> over time unsurprisingly result in the evolution of corresponding Good
> Things to fix the Bad Things (think tumor suppressor genes).
>
> Does the more complex network that results from selections for fitness
> relative to oncogenesis (and other regulatory deficiencies) itself have
> greater potential to evolve? Are things like our big ol' brains in part
the
> product of many years of evolving around regulatory deficiencies? "I
> suffered from Lesch-Nyhan syndrome and all I got was this Broca's region!"
>
> Nah. Too weird and speculative and stupid. For now.
well, the argument from bad design is fun, i guess,
however it has several deficiencies.
1) it's a strawman. few ID'rs claim the paleyesque
'best of all possible worlds' design scenario. ray
bohlin has a reference on his website about the
'whimsy' of the Creator. this doesn't really count,
because nowhere do i find where he says the
designer's product is perfect from the human point
of view. so now you are off the track with, 'well,
you are misrepresenting my position.' while you
spend time in that argument, you lose the civilians.
2) it's a sideshow. you now have opened up the
opportunity to discuss whether the design is indeed
defective. two problems -- first, you may be perceived
as taking the argument from design seriously. this is
a Very Bad Thing, imv, because it provides a gloss,
however small, of legitimacy. second, you get involved
in the esoteric details of the design scenario. again,
you have confused and lost the civilians.
3) it can be considered offensive. if you do not clearly
differentiated between the theological proposition of
generic design and beauty in nature, as understood by
mainline christians, and Intelligent Design, the
proposition that we may observe God's fingerprints in
this or that phenomenum. now someone who does not
understand that you are talking about Intelligent Design
and not the design of Creation thinks you are slagging
their religion. you have alienated and lost the civilians.
4) this is not a new argument. this is an extension of
the argument from suffering as a dis-proof of God to
biological concepts. this argument is so common that
there are simply reams of apologetics designed to rebut
the argument. now you are arguing outside of your
own area of expertise, and arguing about religion (not
science) in an apologetic engagement, and you have
again lost the civilians who don't find you credible on
this issue (not least because you seem unaware of the
reams and reams of apologetics that they have read,
are aware of, and maybe accept).
in short, you're a jet in shark's territory. to the
extent that you bring up the pattern of evolution to
compensate for the Bad Things That Happen,
and demonstrate the causal link, that is a productive
line of thought. however, again, a bit esoteric,
and difficult to explain why wouldn't the designer
have done it that way as well, to someone that
already has a commitment to generic design (not
necessarily Intelligent Design).
--
I'm standing on the outside of your shelter,
Lookin' in,
While the bombs are here a-droppin'
everywhere ...
Have I ever told you that I care?
(Shel Silverstein)
>
>
Sean Pitman
>
> Dear Expired Canine
>
> I have been following this discussion. Sort of. And I was wondering
> would Bcr/Abl or Ret/PTC chimeric proteins qualify as an example to
> the good Dr. Pitman? Both are the results of recombination (chromosome
> translocation) and both result in the induction of novel signaling
> pathways, among other novel functions. Both fusion genes cause cancer
> in humans (chronic myeloid leukemia in the case of Bcr/Abl and
> medullary thyroid carcinoma for Ret/PTC). Bcr/Abl is >1500 aa long,
> Ret/PTC is > than 1200 aa, depending on isotype of Ret.
>
> Wot you think?
Mutations such as the BCR/ABL translocation between chromosomes 22 and
9 are very interesting. Bcr-Abl is a chimeric protein usually
consisting of the amino terminal 927 amino acids (p210) or the amino
terminal 426 amino acids (p190) of Bcr (breakpoint cluster region)
fused to the second exon of the tyrosine kinase Abl (there are also a
few other potential though less common breakpoints in the Bcr region
and even in the Abl region).
The normal abl kinase has the function of modifying proteins by adding
phosphate to the amino acid tyrosine. This protein is a tightly
regulated tyrosine kinase that is predominantly nuclear in
hematopoietic cells. It has 1130-1143 amino acids and 4 domains.
Phosphorylation of tyrosines is one method by which proteins are
switched from inactive states to active states. Amino acids 381-409
are called the "activation loop". This region is highly conserved in
the family of tyrosine kinase proteins.
The normal bcr protein is also a cytoplasmic kinase with
serine/threonine kinase activity. It is composed of 1271 amino acids
and has 5 domains.
The new fusion protein bcr-abl has an increased kinase function. The
altered kinase function of the new bcr-abl kinase controls the
transformation of a normal blood cell into a cancer cell. The various
known bcr-abl isoforms usually have the same c-abl sequence structure
(with loss of the first abl exon), but may differ in their n-terminal
truncated bcr sequences. This usually involves around 426 or 927
amino acids from bcr (but may be as few as 60 or 70aa) added to the
remaining 900 or so abl amino acids for a total of between 1000 to
1800 amino acids.
In order to understand the function of the chimeric bcr-abl protein it
is helpful to understand how the normal abl tyrosine kinase function
works. Normally a 3BP1 binding protein binds to the normal abl
protein on its SH3 domain. This prevents the activation of the SH1
domain, which has a self-phosphorylable tyrosine. However, the
bcr-able chimeric protein, the first n-terminal exon coded region of
bcr binds to the SH2 domain and hides the SH3 domain. As a
consequence, the 3BP1 binding protein cannot bind to the SH3 domain
and so the SH1 domain remains active on the abl protein. This active
domain activates the RAS signal transduction pathway as well as the
MYC pathway, both of which are involved with oncogenesis.
So, what is happening here is that the normal function of one of the
domains of the abl protein is being enhanced by a block to a domain
that normally binds an inhibitor protein. It is relatively easy to
block a function and therefore cause whatever effect that might
follow. In fact, there are many different ways to enhance the kinase
function of the abl protein and the minimum amino acid requirement to
do so is not that great (probably significantly less than 60aa). The
addition of various bcr sequences ranging from 60 or so amino acids to
over 900aa is not the only way either. Several other translocations
give rise to chimeric proteins that deregulate the kinase function.
Of course, these types of mutations do not really creation a new
function at all, but simply deregulate a pre-established function.
The tyrosine kinase function of the abl protein was already there,
preformed, before its function became enhanced. A relatively small
piece of the bcr protein came along and got stuck to it in such a way
that it blocked part of the abl protein's normal function, thus
deregulating it and causing a marked increase in kinase activity and
ultimate deregulation of several different growth related pathways in
the cell. Notice also that such deregulation results in a selectably
non-beneficial result (i.e., cancer). In fact, a significant number of
cancers are the result of protein kinase deregulation.
In short, the bcr-abl chimeric protein is not a new type of function
nor is it a beneficial enhancement of an old function. It in no way
defeats my claim that novel beneficial protein functions above a few
thousand amino acids cannot evolve via mindless evolutionary
processes.
Sean
www.naturalselection.0catch.com
Online References:
http://www.infobiogen.fr/services/chromcancer/Genes/ABL.html
http://www.bloodjournal.org/cgi/content/full/100/3/1092
http://www.rpc.msoe.edu/cbm2/ablopen.html
http://www.sigmaaldrich.com/sigma/rbi-handbook/sg_ls_cs_rbibook_tyrosine.pdf
http://www.infobiogen.fr/services/chromcancer/Anomalies/t0922ANL.html
http://www.bloodjournal.org/cgi/content/full/99/8/2957
http://www.infobiogen.fr/services/chromcancer/Genes/ABL.html
http://www.nature.com/cgi-taf/DynaPage.taf?file=/onc/journal/v15/n14/abs/1201342a.html&dynoptions=doi1070713813
Ian Musgrave & Peta O'Donohue
Address altered to avoid spam, delete RemoveInsert
On Sat, 6 Dec 2003 15:34:00 +0000 (UTC),
seanpi...@naturalselection.0catch.com (Sean Pitman) wrote:
>unre...@hotmail.com (MEC) wrote in message news:<c240c53.03120...@posting.google.com>...
>> Dear Expired Canine
>>
>> I have been following this discussion. Sort of. And I was wondering
>> would Bcr/Abl or Ret/PTC chimeric proteins qualify as an example to
>> the good Dr. Pitman? Both are the results of recombination (chromosome
>> translocation) and both result in the induction of novel signaling
>> pathways, among other novel functions. Both fusion genes cause cancer
>> in humans (chronic myeloid leukemia in the case of Bcr/Abl and
>> medullary thyroid carcinoma for Ret/PTC). Bcr/Abl is >1500 aa long,
>> Ret/PTC is > than 1200 aa, depending on isotype of Ret.
>>
>> Wot you think?
>
>Mutations such as the BCR/ABL translocation between chromosomes 22 and
>9 are very interesting. Bcr-Abl is a chimeric protein usually
>consisting of the amino terminal 927 amino acids (p210) or the amino
>terminal 426 amino acids (p190) of Bcr (breakpoint cluster region)
>fused to the second exon of the tyrosine kinase Abl (there are also a
>few other potential though less common breakpoints in the Bcr region
>and even in the Abl region).
[big snip of reasonable summary of BCR-ABL, except for the fact
BCR-ABL is still under inactivation control, and the inhibitor peptide
loop still flips between the active and inactive form. In fact, the
BCR-ABL inhibitor and anti-cancer drug glivec works by binding to the
INactive form of BCR-ABL and freezing it in the inactive form]
>In short, the bcr-abl chimeric protein is not a new type of function
>nor is it a beneficial enhancement of an old function. It in no way
>defeats my claim that novel beneficial protein functions above a few
>thousand amino acids cannot evolve via mindless evolutionary
>processes.
See, I predicted this "it is not complex enough" response didn't I.
But here is Dr. Pitmans original claim
> > I have predicted that no mindless process will ever be
> > able to create anything new within a given level of complexity or
> > beyond in real time. I have drawn this line at several thousand amino
> > acids working at the same time.
His current response does involve a slight shifting of goal posts. In
the original statement it was "Anything new" which is not the same as
"novel beneficial protein functions".
Be that as it may, there is an equivocation over "novel function". Dr.
Pitman feels BRC-ABL doesn't count because it is not a "new type of
function", BCR-ABL is a tyrosine kinase link ABL is. However, it has
new targeting (cytoplasm) and new substrates (which plays a
substantial role in it being a cancer gene). For many of the systems
in organisms, novelty comes not from changes in reaction mechanism,
but from targeting and substrate changes.
As a case in point, the lactase which Dr. Pitman bangs on about has
the same reaction _mechanism_ as sugar metabolizing enzymes, but can
accommodate a different substrate (beta-galactoside sugars).
This raises another issue, Dr. Pitman repeatedly confuses size with
"complexity". Lactase is a big enzyme, but it doesn't do anything
particularly complex. When Dr. Pitman says
>Yes, like the lactase and nylonase enzymes, which requires no more
>than 480 or so amino acids in a fairly flexible order at minimum.
>Nothing much higher than this level of complexity has ever been shown
>to evolve.
We are left confused as to what he means "nothing much higher than
this level of complexity has been shown to evolve", if size is not an
issue, why has he drawn a size limit (and the BCR-ABL gene shows that
1,800 aa long functional enzymes with different targeting and
substrate functions can evolve). What does he mean by "complexity"?
Able to perform multiple reactions? There are many enzymes that have
been evolved that perform multiple reactions (Bary Hall has
experimentally evolved such enzymes). What then?
What about "molecular machines" like the flagella and the F1F0 atpase.
They don't fit his criteria, as they are not large proteins, but
non-covalent associations of multiple small subunits. Even the
impressive, long flagellar whip is not a single, big protein, but made
up of thousands of much smaller subunits which self assemble in a
non-covalent manner into the long structure.
So the whole issue of "several thousand amino acids working at the
same time." is completely irrelevant.
Cheers! Ian
=====================================================
Ian Musgrave Peta O'Donohue,Jack Francis,Michael James and Andrew Thomas Musgrave
reynella@RemoveInsret_werple.mira.net.au http://home.mira.net/~reynella/
Sean Pitman
below):
sweetnes...@yahoo.com wrote in message news:<4d71d185.03120...@posting.google.com>...
> I have presented you with proof (laboratory proof, in many instances)
> that your statements are incorrect.
You have shown that short amino acid sequences can come together to
form a new unified function that is indeed unique and of greater
complexity. The only problem you have here is that the minimum amino
acid number required for your most complex example is only 3 or 4
hundred amino acids. My argument is that evolution becomes more and
more difficult the greater the minimum amino acid requirement until it
becomes impossible this side of zillions of years when the minimum
requirement reaches a few thousand amino acids in fairly specified
order. Where are your examples of evolution requiring such a level of
minimum amino acid specificity? I see a lot of hot air coming from
you, but no such example. Where is the reference for such a
demonstration? And, by the way, your lame bacterial swarming example
doesn't even come close (see discussion below).
Recently I have been referred to the example of the bcr-abl chimeric
protein that causes various forms of leukemia such as chronic
myelogenous leukemia. The reason for this referral is the fact that
the bcr-abl function is generally realized with the use of between
1000 and 1800 amino acids. This is good thinking since it is actually
an attempt to controvert my hypothesis whereas you haven't even tried
to present the de novo evolution of anything with a minimum function
requiring over a few hundred amino acids working together at the same
time.
But, before you become excited about the bcr-abl function, there is a
little problem in that it really isn't a new type of function or is it
a selectably beneficial function, but is based on the deregulation of
the pre-established kinase function of the abl protein. For a more
detailed discussion of bcr-abl function see:
http://groups.google.com/groups?hl=en&lr=&ie=UTF-8&selm=80d0c26f.0312060737.24b46c30%40posting.google.com
> I have provided you with at least three examples of exactly that
> happening: simpler systems combining to produce a novel, complex
> system with a different, novel function. The fact that there are more
> ways to combine systems nonfunctionally does not have a bearing on
> this.
Actually it has everything to do with this. What you have shown are
simpler systems combining to produce a novel function that requires,
at minimum, only 3 or 4 hundred amino acids. You have also provided
examples of a simple function requiring less than a few hundred amino
acids at minimum evolving a new type of function within the same level
of complexity, but not anything much greater. Please, I think you can
at least try and do better than this.
> The system does not work by searching randomly through
> thousands of different combinations of amino-acids, until it "hits"
> the right combination. This has been explained to you over and over
> again. It simply does not happen, and your refutation of this does not
> refute anything that is a part of evolutionary theory.
You haven't explained how my ideas are wrong in this regard. All you
have shown is how the same type of function can be up-regulated and
down-regulated (See discussion below of Myxococcus xanthus swarming
evolution demonstrated by Gregory J. Velicer and Yuen-tsu N. Yu of the
Max Planck Institute for Developmental Biology) but not how new types
of function within higher levels of complexity can be evolved without
searching randomly through a very large non-beneficial sequence space.
Sequences with the same types of functions can be clustered around
each other like little islands of stepping stones - very much like a
sentence who's individual letters can be rearranged somewhat without a
complete loss of beneficial meaning, but who's type of meaning is
fairly isolated from other sentences with different types of meaning
or significantly different ways of achieving the same meaning. How to
cross the non-beneficial gap between these two different types of
meaning? That is the question? For shorter sequences, the random
walk required is easier to overcome. However, with each amino acid
increase in the minimum random walk required to achieve the success of
any new type of beneficial function within that level of functional
complexity, the time required grows exponentially.
> Please show me how would it be possible for a change in biological
> systems, such as it happens NOW, at this moment, to go on for, say,
> ten thousand years, WITHOUT producing a novel, complex system?
Ok - take, for example, a particular function that requires, at
minimum 5,000aa at minimum to be realized. Say this sequence happens
to get duplicated so that it can undergo various mutations without
risking significant loss to the original beneficial function (which
has been optimized for its host by now - as far as *level* of function
is concerned). The sequence space at this level of complexity is more
than 10e6500 sequences. The question is, out of all of these
universes of possibilities, how many are or would be beneficial to the
given organism in question? If the organism could use a million
different types of functio