dynein evolution
Nick Tamzek
Howdy t.o.-ers,
The ID debate over at the Chronicle of Higher Education website
(which published some articles on the ID movement in late December,
see:
http://chronicle.com/free/v48/i17/17a00801.htm
http://chronicle.com/colloquy/2001/design/design.htm
http://chronicle.com/colloquy/2001/design/re.htm )
has finally about wound down after 300+ posts, probably the most
active colloquy they've had (they have one every week, the other few
that I've checked get only a few posts).
Anyhow, I felt like someone had to add some biology back into the
discussion (which was getting very philosophical, not a bad thing but
not the whole story), so I wrote a number of posts:
http://chronicle.com/colloquy/2001/design/40.htm
http://chronicle.com/colloquy/2001/design/99.htm
http://chronicle.com/colloquy/2001/design/152.htm
http://chronicle.com/colloquy/2001/design/153.htm
http://chronicle.com/colloquy/2001/design/267.htm
http://chronicle.com/colloquy/2001/design/268.htm
http://chronicle.com/colloquy/2001/design/269.htm
http://chronicle.com/colloquy/2001/design/270.htm
http://chronicle.com/colloquy/2001/design/280.htm
http://chronicle.com/colloquy/2001/design/293.htm
...most of which is not particularly original and which most of you
will be familiar with, although they might serve as handy "pages o'
links". I just wanted to point out one new tidbit I came across that
seems relevant to the evolution of one of Behe's systems (the
eukaryotic cilium) as well as being a particularly elegant case of
"How to evolve IC":
http://chronicle.com/colloquy/2001/design/269.htm
...which is about (the later bit of the post) about recent scientific
work on identifying simpler homologs to the dynein heavy chain (the
"motor" of dynein), one of the biggest proteins around. I'll repost
the bit on dynein here, to see if there are comments (particularly
from someone who knows more about this example, I wouldn't be
surprised on t.o.), and perhaps for future reference as a particularly
good case of the evolution of "strict" IC (multiple parts required AND
interacting with each other AND well-matched AND machine-like --
dynein is described as the "Mack truck of the intracellular
interstate" [1] by one science writer).
The basic idea for the evolution of IC here is the specialization of
originally identical components (a simple prokaryotic homolog of
dynein is a hexamer, wherein six identical proteins from one gene form
a six-part ring) resulting in complexes with functions different than
the original. This is something that is familiar in metazoan biology
(e.g. specialization of segments), but not really in biochemical
evolution (to my very limited knowledge; perhaps the "duplicate genes
to extend a metabolic pathway" idea is a version of this. And
actually, now that I'm thinking about it, hemoglobin sort of is, also,
being made up of myoglobin-like subunits, although the specialization
is limited in this case, although on the other hand the cooperative
properties almost certainly are crucial to the "effective functioning"
of hemoglobin, so if Behe were consistent he would not exclude
hemoglobin from his IC classification -- but this is another debate).
I post the relevant bit here in case the CHE board gets deleted and to
see if people have comments/additional useful factoids/can find holes
in the argument:
[begin]
[T]he failure of IDists to address actual biology will not deter me
from posting more of it. While playing around on PubMed over the
break, I came across a fascinating article that shows yet another way
that IC, and even machine-like IC, can evolve.
Here is the article:
Mocz G, Gibbons IR. "Model for the motor component of dynein heavy
chain based on homology to the AAA family of oligomeric ATPases."
Structure (Camb) 2001 Feb 7;9(2):93-103
http://www.ncbi.nlm.nih.gov/entrez/query.fcgicmd=Retrieve&db=PubMed&list_uid
s=11250194&dopt=Abstract
I will attempt to give a summary of the conclusions for those readers
who may have missed biochemistry day in kindergarten ;-) , so that the
article excerpt that I quote will make some sense.
Those who have read Behe's book, Darwin's Black Box, may recall that
Behe's first example of an IC biochemical structure was the eukaryotic
cilium, discussed in his chapter "Row, row, row your boat." He
describes three main, key components of the cilium: tubulin (which
forms the microtubules of the axoneme, the 'rod' of the cilium),
dynein (which is the motor which moves the microtubules past each
other), and nexin (which keeps the microtubules from sliding apart,
which results in the bending motion of the cilium).
I posted some references on the origin of the cilium in post #153.
Some of those references discussed the relationship between the
simpler cytoplasmic dynein and the more complex cilial dynein. But
where did cytoplasmic dynein come from? The most common scientific
view of the relationship between eukaryotes (large cells with a
cytoskeleton and nucleus) and prokaryotes (smaller, simpler cells with
no nucleus and only recently discovered to have a simple cytoskeleton;
eubacterial and archaea are the two fundamental groups of prokaryotes)
appears to be (there is still much debate) that eukaryotes are derived
from prokaryotes. Specifically, the 'core' 'informational' genes of
eukaryotes are derived from a direct archaeal ancestor, and that many
of the current eukaryotic 'metabolic' genes are derived via lateral
transfer from eubacteria, something that has people like DI IDist
Jonathan Wells proclaiming the end of the 'Tree of Life' model, even
though it has been widely accepted since the early 1980's that the
mitochondria and chloroplasts of eukaryotes are in fact the
descendents of endosymbiotic eubacteria, and that many of the symbiont
genes have been transferred to the eukaryotic nucleus.
Anyhow, if eukaryotes did in fact evolve from prokaryotes (instead of
being specially created, as Todd Moody would apparently have it),
there ought to be evidence of this process in the form of prokaryotic
homologs to 'key' eukaryotic genes, for example the genes of the
eukaryotic cytoskeleton, one of the most distinct features of
eukaryotes. Such a homolog for tubulin was long suspected in the
prokaryotic cell-division protein FtsZ, a suspicion which was
dramatically confirmed by the independent solution of the structures
of FtsZ and tubulin. See these webpages:
On the evolution of tubulin:
http://www.cellbio.duke.edu/Faculty/~Erickson/FtsZ_tubulin_struct.html
http://octem.berkeley.edu/webpage/papers/nature/index.html
& this article:
Faguy, D. M. and Doolittle, W. F. (1998). "Cytoskeletal proteins: The
evolution of cell division." Current Biology, V8(N10): R338-R341.
Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=
PubMed&list_uids=9601632&dopt=Abstract
Dynein, however, is a tougher case. It is routinely referred to as a
'motor' protein, and in fact it is one of the biggest and most complex
proteins known. It powers the cilium, but other versions of the dynein
protein are used to push microtubules apart from each other during
mitosis (eukaryotic cell division), and to carry cargo along
microtubules.
The actual 'motor' of dynein is found in the 'dynein heavy chain'
(DHC). Various other dynein chains (referred to as light and
intermediate, depending on their size) perform regulatory roles (and
perhaps other functions; the newly-evolved Drosophila sperm dynein
intermediate chain gene, Sdic, has an unknown but evidently highly
selectable function; see refs in #153).
The problem was that, until recently, there was no likely prokaryotic
homolog to the dynein heavy chain. Indeed, what use would prokaryotes
have for dynein, having no cilia, mitosis, or long-distance transport
needs, or even any microtubules? It will not surprise biologists to
discover that the prokaryotic homolog has, in fact, an entirely
different function, and is structurally much simpler.
The Mocz and Gibbons (2001) paper identifies the homolog of dynein as
AAA ATPases (AAA stands for ATPases Associated with cellular
Activities; don't ask me why it's not AAWCA, I don't know). ATP is the
main energy molecule of the cell, and an ATPase is an enzyme that
breaks down ATP, releasing energy that can be used for work. Dynein
burns ATP to do its work also.
The various proteins in the AAA ATPase family have a number of
functions (click the 'related articles' button in the PubMed link,
above), but the interesting thing about them is their structure. The
simplest AAA ATPases actually have a symmetric ring shape, and are
actually made by a self-assembled hexamer of one protein -- that is,
one gene produces one protein, and six copies of this (wedge-shaped)
protein form a ring (hexa = six). Since all six 'parts' are in fact
identical, there is really no crucial 'part' -- remove one of the
subunits of the ring, and the same gene can produce an identical
replacement. One part only, so no IC here.
However, other AAA ATPases are more complex. Some AAA ATPases are
coded for by *six* genes, arrayed next to each other along the
chromosome. Six copies of the gene can occur very simply by gene
duplication; what is interesting about this situation is that the
duplication allows each copy to evolvely independently, and therefore
to specialize to perform nonuniform functions in the AAA ATPase ring.
Mocz and Gibbons (2001) note that in one AAA ATPase "this
differentiation of AAA modules has progressed to the point that the
deletion of the gene encoding any one of the six is lethal, indicating
that the individual subunits, although closely related in sequence,
are functionally noninterchangeable." If you blinked, you might have
missed it: we just moved from non-IC to IC using very simple, well
understood genetic processes -- and we're not even at dynein yet!
So where does dynein come it? Well, it turns out that the dynein heavy
chain, which is coded by a single large gene, has six AAA-like domains
in it. This can be easily explained if the genes of a six-gene,
asymmetric ATPase were merged into one huge gene. And once this has
occurred, additional complexities can evolve. To cut to the chase, in
their conclusion Mocz and Gibbons (2001) write:
======
"In the dynein heavy chain, the fusion of the six AAA modules into a
single polypeptide has permitted the hexameric assembly to evolve even
greater structural and functional asymmetry, including the acquisition
of the two substantial accessory structures that protude from the
motor unit. One of these acquired structures, formed from the region
of the dynein heavy chain between D4 and D5, comprises the 100 A stalk
with predicted [alpha]-helica coiled-coil configuration that supports
the all-important ATP-sensitive microtubule binding site [12]. The
second is formed by the approximately 1800 residue extension onto the
N terminus of D1 that comprises the tail component of the complete
dynein heavy chain. The substantial [alpha]-helical component in these
accessory structures suggests that they may both have evolved through
a gradual extension and specialization of the much shorter
coiled-coil/leucine-zipper structure often found in the N-terminal
region of AAA proteins [43, 44]. Interestingly, the microtubule
binding domain of katanin also involves an N-terminal extension from
its AAA structure [35]. However, an alternative possibility is that
the microtubule binding stalk evolved by prolongation of helices H6
and H7, which form a short leucine-zipper-like structure in the C
domain of our present models, where it has been inherited from the
NSF-D2 template."
======
In the simple AAA ATPase, all of the 6 subunits could hydrolyze ATP.
But interestingly, in dynein, one of the former genes (now a single
domain of the six-domain dynein protein, labeed D1) has specialized to
do the ATP hydrolysis, and the other domains act to help transmit the
resulting mechanical energy to the power stroke of the stalk:
======
"Concomitant with the development of its asymmetrical structure, the
dynein motor unit has evolved a functional dominance of the D1 module,
which alone has retained the full ability for binding and hydrolysis
of ATP [28]. Unlike the balanced extension of differential function
that appears to have occurred in the proteasome regulator subunits
during evolutionary passage from archaebacteria to eukaryotes [39,
45], the other AAA modules in dynein heavy chains appear to have
progressively lost much of their typical AAA function because they
became fused into a single polypeptide. As discussed above, modules
D2, D3, and D4 appear to have lost their capability for ATP
hydrolysis, and the most degenerate modules, D5 and D6, show no
significant binding of ATP. The partial loss of active function in
five of its AAA modules not withstanding, the dynein motor appears to
require the presence of all its AAA modules for functional activity.
Expression constructs lacking any of the AAA modules, or even the
region of the tail component adjacent to D1 (residues 1400-1813),
appear to show no ATPase activity [11, 46]. This requirement for
structural integrity of the dynein motor unit resembles that of other
members of the oligomeric ATPase class and may indicate that
cooperative interactions of module D1 with the other AAA modules play
an essential role in transferring the energy made available at the
hydrolytic ATP binding site in D1 to the microtubule binding site
attached between D4 and D5."
======
For those of you who were waiting for the short-short version, here's
a rough summary of the evolutionary model proposed by Mocz and Gibbon:
Key:
G = gene
P = individual protein
D = domain (subunit of a gene)
X = extension of a section of a gene/protein
Starting point: G --> P (a simple, stand alone ATPase)
Step 1: G --> PPPPPP (a hexamer ring of 6 identical subunits)
Step 2: GGGGGG --> PPPPPP (the genes have been duplicated sixfold)
Step 3: G1-G2-G3-G4-G5-G6 --> P1-P2-P3-P4-P5-P6 (the genes have
diverged, producing an IC machine with six necessary,
noninterchangable, and necessarily interacting and well-matched parts)
Step 4: D1-D2-D3-D4-D5-D6 --> 'proto-dynein' (could have the same
function as the protein in previous step; the 6 genes have been
concatenated into one big gene with six necessary domains,
specialization of the domains continues)
Step 5: D1-D2-D3-D4-X1-D5-D6-X2 --> dynein heavy chain (this is the
dynein heavy chain; two interdomain extensions have evolved)
So, we've got a reasonably good and detailed outline for the origin of
the dynein motor. It should be emphasized that the 'steps' are really
major stages; for example, the duplication and diversification of
G1-G6 genes could have occurred one by one; one gene duplicates and
diverages via point mutation, then another. The genes could have been
linked into domains one-by-one, also, etc. So the number of discrete
'steps' would be very much greater. But notice that no processes other
than (a) gene duplication and (b) gradual optimization via NS of small
mutations needed to be invoked.
Certainly this is still just a general outline, and will need much
development and testing in further research. But if we compare the
above discussion to what Behe would have written (all that he could
have written, more precisely), if he'd written the Mocz & Gibbons
paper:
Step 1: IDdidit.
Or perhaps, Step 1: [poof] Dynein.
To paraphrase a famous quote from someone-or-other, "we have no need
of that hypothesis."
I recommend that papers like this be cited as often as possible until
Behe or a Behe defender show why they don't constitute direct
refutation of his argument.
PS: If you check out these two papers:
Gibbons, I. R. (1995). "Dynein family of motor proteins: Present
status and future questions." Cell Motility and the Cytoskeleton,
32(2): 136-144. Link:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed
&list_uids=8681396&dopt=Abstract
Asai, D. J. and Koonce, M. F. (2001). "The dynein heavy chain:
structure, mechanics and evolution." Trends in Cell Biology, V11(N5):
196-202. Link: http://www.sciencedirect.com/science/journal/09628924
...you will discover, hopefully not to your surprise at this point,
that a similar process can be traced in the evolution of cilial dynein
from cytoplasmic dynein. To wit, cytoplasmic dynein usually occurs as
a homodimer (two identical subunits encoded by one gene):
Cytoplasmic dynein: dynein heavy chain gene --> dyneinHC-dyneinHC
...but, in cilial dynein, the DHCs appear as heterodimers or
heterotrimers (two or three distinct dynein heavy chains), e.g.:
Cilial dynein: DHC gene1, DHC gene1, --> DHC1-DHC2
...and there is even a subfamily of DHCs, DYH1B, that is
'transitional' in that it closer to cytoplasmic dyneins in sequence,
but has a cilial function more similar to that of the cilial dyneins,
indicating that the cytoplasmic-->cilial transition may be happening
again.
PPS: I can't resist posting one more bit. It is commonly argued by ID
supporters that evolution has little relevance or application to
fields outside of evolutionary biology. This is just plain false, and
is especially surprising coming from people who often talk like they
know a lot about biological information and functional complexity.
Bioinformatics, genomics and protenomics rely fundamentally on the
concepts of common descent and homology, which allow the crucial
insight "if X is related to Y, then something that we already know
about X may help us in figuring out how Y works". And exactly this
logic is used in the Mocz and Gibbons (2001) paper, X being AAA
ATPases, and Y being dynein. The exact mechanism by which ATP
hydrolysis results in mechanical energy is still undetermined. But
Mocz and Gibbons are able to use the evolutionary insight to propose a
functional model for dynein:
======
Biological Implications: The structural resemblance of the dynein
motor to the hexameric assembly of AAA modules in the hsp100
chaperones and the regulator/translocator component of proteasomes and
their bacterial equivalents [32, 39] suggests that the mechanism by
which the energy released at the hydrolytic ATP binding site of dynein
becomes transferred to the [alpha]-helical stalk supporting the
microtubule binding site on the opposite side of the motor may be
related to the ATP-dependent mechanism by which extended polypeptides
become translocated into the interior compartment of chaperones and
proteasomes. In HslU, the eubacterial proteasome
regulator/translocator, the presence of ATP or a nonhydrolytic ATP
analog at the nucleotide binding site results in flexing at a hinge
region between the N and C domains, with a decrease of approximately
15 [degrees] in the interdomain angle [21]. A similar flexing between
the N and C domains of the enzymatically active D1 module in dynein
may represent one of the intial events in the mechanochemical cycle
coupled to ATP binding and hydrolysis in the dynein motor and would
correspond to a local linear displacement of 10 to 15 A within the D1
module. This displacement is substantially smaller than the observed
step size of 80 A with which dynein translocates along a microtubule
[47]. Although up to about half of the necessary amplification of
displacement can be accounted for by the extended lever arm that
results from the attachment of the microtubule binding site between
the D4 and D5 modules on the opposite side of the hexagonal assembly
from D1, it is improbable that this can account for all of it.
Additional amplification may be contributed by cooperative
interactions of the hydrolytic D1 module with the nonhydrolytic D2,
D3, and D4 modules that change the interdomain angles of the latter,
possibly by modifying their affinity for binding ATP. Interestingly,
the hexameric assembly of HslU shows evidence of negative
cooperativity of nucleoide binding in adjacent AAA modules, with only
three or four of the six able to bind a nonhydrolyzable ATP analog
concurrently [21]. A similar cooperativity of ATP binding among the
D1, D2, D3, and D4 modules of dynein [14] may contributee to the
amplification of linear displacement, as well as underlie the
demonstrated ability of the axonemal dynein motor to generate
autonomous oscillatory motion when subjected to stretch activation.
Such stretch-activated oscillation may be involved in the mechanism by
which dynein generates oscillatory beating in cilia and sperm flagella
[48, 49].
======
This is an insight Mocz and Gibbon would have lost if they had been
satisfied with "IDdidit."
[end]
[1] An slightly dated article (pre-dating the homology work in 2000
and 2001) on dynein research, this is a good brief intro to some of
what is going on:
http://www.wadsworth.org/publish/biofocus/oct98/hood.htm
Thanks, Nic Tamzek
niiic...@yahoo.com
Howard Hershey
Nick Tamzek wrote:
Methinks we have a candidate for the next P-o-M.
John Wilkins
> Nick Tamzek wrote:
>
> Methinks we have a candidate for the next P-o-M.
Seconded and voted for.
--
John Wilkins
Occasionally making sense for over 46 years
Noelie S. Alito
method of getting PotM Man's attention is putting "PotM" in
the subject line.)
Noelie Alito
Second Attache to the Deputy Minister of Protocol
Bureau of Newsgroup Propriety
"John Wilkins" <john.w...@bigpond.com> wrote in message
news:1f6azex.1msl1sx9k546qN%john.w...@bigpond.com...
Ian Musgrave & Peta O'Donohue
Address altered to avoid spam, delete RemoveInsert
On 19 Jan 2002 19:19:26 -0500, john.w...@bigpond.com (John Wilkins)
wrote:
>Howard Hershey <hers...@indiana.edu> wrote:
>
>> Nick Tamzek wrote:
>>
>> Methinks we have a candidate for the next P-o-M.
>
>Seconded and voted for.
Thirded and also voted for. Great post (but then, I'm biased towards
molecular biology.
Cheers! Ian
=====================================================
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
John Wilkins
> Did either of youse guys mail in the nomination? (The alternative
> method of getting PotM Man's attention is putting "PotM" in
> the subject line.)
>
>
> Noelie Alito
> Second Attache to the Deputy Minister of Protocol
> Bureau of Newsgroup Propriety
Sorry, mum.
>
>
> "John Wilkins" <john.w...@bigpond.com> wrote in message
> news:1f6azex.1msl1sx9k546qN%john.w...@bigpond.com...
> > Howard Hershey <hers...@indiana.edu> wrote:
> >
> > > Nick Tamzek wrote:
> > >
> > > Methinks we have a candidate for the next P-o-M.
> >
> > Seconded and voted for.
Howard Hershey
"Noelie S. Alito" wrote:
>
> Did either of youse guys mail in the nomination? (The alternative
> method of getting PotM Man's attention is putting "PotM" in
> the subject line.)
I choose the later method, since you have so kindly obliged.
Never was too much on the protocol of the P-o-M thing.
>
> Noelie Alito
> Second Attache to the Deputy Minister of Protocol
> Bureau of Newsgroup Propriety
>
> "John Wilkins" <john.w...@bigpond.com> wrote in message
> news:1f6azex.1msl1sx9k546qN%john.w...@bigpond.com...
> > Howard Hershey <hers...@indiana.edu> wrote:
> >
> > > Nick Tamzek wrote:
> > >
> > > Methinks we have a candidate for the next P-o-M.
> >
> > Seconded and voted for.
Firsted and now voted for.
Frank J
"Howard Hershey" <hers...@indiana.edu> wrote in message
news:3C4921D9...@indiana.edu...
>
>
> Nick Tamzek wrote:
>
> Methinks we have a candidate for the next P-o-M.
> >
(snip)
Nick has my vote too. Now that we have established in another thread that
Behe probably has more research funding than the average evolutionary
biologist, we can look forward to his alternative mechanism instead of
another sales pitch for ID.
zosdad
> "Howard Hershey" <hers...@indiana.edu> wrote in message
> news:3C4921D9...@indiana.edu...
> >
> >
> > Nick Tamzek wrote:
> >
> > Methinks we have a candidate for the next P-o-M.
> > >
>
Hey, thanks for the comments. Actually, I've been inspired to expand
a bit, heading towards a FAQ perhaps. See below.
> (snip)
>
> Nick has my vote too. Now that we have established in another thread that
> Behe probably has more research funding than the average evolutionary
> biologist,
Eh? Which thread was that?
Here's the latest incarnation. In the HTML version I steal some pics
from articles, but you'll have to use your imagination or look at the
articles via PubMed...
Begin paste
=======
The Evolution of the Dynein Heavy Chain and the AAA+ ATPase
Superfamily
by Nic Tamzek
Copyright © 2002
[posted [draft]: 1/2002]
Introduction
The Evolution of the Dynein Heavy Chain (DHC)
Summary
The Evolution of Cilial (axoneme) Dynein from Cytoplasmic Dynein
The Practical Results of Evolutionary Theory for Dynein Research
Endnotes
References
Introduction
I would like to point out one new tidbit of research that I've come
across that seems relevant to the evolution of one of Behe's systems
(the eukaryotic cilium) and is a particularly elegant case of "How to
evolve irreducible complexity (IC)" unto itself. This material was
originally developed as a post for the Chronicle of Higher Education
(CHE) discussion on CHE's December 21, 2001 article on Intelligent
Design entitled "Darwinism Under Attack."
I would like to briefly review recent scientific work on identifying
simpler homologs to the dynein heavy chain (the "motor" of dynein),
literally one of the largest, most complex, and most important
proteins known. I see it as a particularly good case of the evolution
of "strict IC" ("strict IC" having not only "multiple parts required
for function," but having a system with multiple parts required AND
interacting with each other AND well-matched AND machine-like; this is
important as IDists, Behe included, are inconsistent on whether
qualifiers beyond "multiple parts required" are really part of the
definition of irreducible complexity).
Dynein (Gibbons and Rowe 1965) is described as the "Mack truck of the
intracellular interstate" by one science writer [1]. Various versions
of dynein have functions like moving the cilium, carrying cargo down
microtubules, and pushing microtubules (and therefore chromosomes)
apart during eukaryotic mitosis (cell division). The Dynein Heavy
Chain (DHC) is universally referred to as the "motor" domain of dynein
[2], and its size and complexity are commented on in the introduction
of every scientific article on the topic. For example, Asai and
Koonce (2001) write,
The dynein heavy chain is enormous, being approximately 4600
amino acid residues in length, more than twice the size of myosin II
and more than four times the mass of conventional kinesin. Unlike
myosin and kinesin, the predicted secondary structure of the dynein
sequence does not readily divide into a globular head and a tail
domain. However, genetic, molecular and structural analyses have
revealed several discrete functional domains, as summarized here (Fig.
1).
We will look at Figure 1 of Asai and Koonce presently.
The basic idea for the evolution of IC here is the specialization of
originally identical components (a simple prokaryotic homolog of
dynein is a hexamer,
wherein six identical proteins from one gene form a six-part ring)
resulting in complexes with functions different than the original.
This is something that is familiar in metazoan biology (e.g.
specialization of segments), but not really in biochemical evolution
(to my very limited knowledge; perhaps the "duplicate genes to extend
a metabolic pathway" idea is a version of this. And actually, now
that I'm thinking about it, hemoglobin sort of is, also, being made up
of myoglobin-like subunits, although the specialization is limited in
this case, although on the other hand the cooperative properties
almost certainly are crucial to the "effective functioning" of
hemoglobin, so if Behe were consistent he would not exclude hemoglobin
from his IC classification -- but this is another debate).
Following is a more detailed review of Mocz and Gibbons (2001), who
provide a model for the origin and evolution of the dynein heavy
chain. This is a
somewhat edited version of my CHE post.
The Evolution of the Dynein Heavy Chain (DHC)
The failure of IDists to address actual biology will not deter me from
posting more of it. While playing around on PubMed over the break, I
came across a fascinating article that shows yet another way that IC,
and even machine-like IC, can evolve.
Here is the article:
Mocz G., Gibbons I.R. (2001) "Model for the motor component of dynein
heavy chain based on homology to the AAA family of oligomeric
ATPases." Structure (Camb). 9(2):93-103.
Here is the link to the PubMed reference, which links to the full-text
article if you have subscription access, for example if at a
university library.
I will attempt to give a summary of the conclusions for those readers
who may have missed biochemistry day in kindergarten ;-) , so that the
article excerpt
that I quote will make some sense.
Those who have read Behe's book, Darwin's Black Box, may recall that
Behe's first example of an IC biochemical structure was the eukaryotic
cilium,
discussed in his chapter "Row, row, row your boat." He describes three
main, key components of the cilium: tubulin (which forms the
microtubules of the
axoneme, the 'rod' of the cilium), dynein (which is the motor which
moves the microtubules past each other), and nexin (which keeps the
microtubules from
sliding apart, which results in the bending motion of the cilium).
I have cited some references on the origin of the cilium elsewhere.
Some of those references discussed the relationship between the
simpler cytoplasmic
dynein and the more complex cilial dynein. But where did cytoplasmic
dynein come from? The most common scientific view of the relationship
between
eukaryotes (large cells with a cytoskeleton and nucleus) and
prokaryotes (smaller, simpler cells with no nucleus and only recently
discovered to have a
simple cytoskeleton; eubacterial and archaea are the two fundamental
groups of prokaryotes) appears to be (there is still much debate) that
eukaryotes are
derived from prokaryotes. Specifically, the 'core' 'informational'
genes of eukaryotes are derived from a direct archaeal ancestor, and
that many of the current eukaryotic 'metabolic' genes are derived via
lateral transfer from eubacteria, something that has people like
Discovery Institute IDist Jonathan Wells proclaiming the end of the
'Tree of Life' model, even though it has been widely accepted since
the early 1980's that the mitochondria and chloroplasts of eukaryotes
are in fact the descendents of endosymbiotic eubacteria, and that many
of the symbiont genes have been transferred to the eukaryotic nucleus.
Anyhow, if eukaryotes did in fact evolve from prokaryotes (instead of
being specially created, as Todd Moody would apparently have it),
there ought to be
evidence of this process in the form of prokaryotic homologs to 'key'
eukaryotic genes, for example the genes of the eukaryotic
cytoskeleton, one of the most distinct features of eukaryotes. Such a
homolog for tubulin was long suspected in the prokaryotic
cell-division protein FtsZ, a suspicion which was
dramatically confirmed by the independent solution of the structures
of FtsZ and tubulin. See these webpages:
On the evolution of tubulin:
http://www.cellbio.duke.edu/Faculty/~Erickson/FtsZ_tubulin_struct.html
http://octem.berkeley.edu/webpage/papers/nature/index.html
...and this article:
Faguy, D. M. and Doolittle, W. F. (1998). "Cytoskeletal proteins: The
evolution of cell division." Current Biology, V8(N10): R338-R341.
PubMed Link.
Dynein, however, is a tougher case. It is routinely referred to as a
'motor' protein, and in fact it is one of the biggest and most complex
proteins known. It powers the cilium, but other versions of the dynein
protein are used to push microtubules apart from each other during
mitosis (eukaryotic cell division), to carry cargo along microtubules,
and probably other functions (see e.g. Vorobjev et al., 2001).
The actual 'motor' of dynein is found in the 'dynein heavy chain'
(DHC). Various other dynein chains (referred to as light and
intermediate, depending on their size) perform positioning and
regulatory roles (and perhaps other functions; the newly-evolved
Drosophila sperm dynein intermediate chain gene, Sdic, has an unknown
but highly selectable function; see Nurminsky et al. 1998, 2001).
The problem was that, until recently, there was no likely prokaryotic
homolog to the dynein heavy chain. Indeed, what use would prokaryotes
have for
dynein, having no cilia, mitosis, or long-distance transport needs, or
even any microtubules? It will not surprise biologists to discover
that the prokaryotic
homolog has, in fact, an entirely different function, and is
structurally much simpler.
The Mocz and Gibbons (2001) paper identifies the homolog of dynein as
AAA ATPases (AAA stands for ATPases Associated with cellular
Activities; don't
ask me why it's not AAWCA, I don't know). ATP is the main energy
molecule of the cell, and an ATPase is an enzyme that breaks down ATP,
releasing
energy that can be used for work. Dynein burns ATP to do its work
also.
The various proteins in the AAA ATPase family have a vast number of
highly divergent functions (see Neuwald et al. 1999, and Ogura and
Wilkinson 2001,
for reviews), but the interesting thing about them is their structure.
The simplest AAA ATPases actually have a symmetric ring shape, and are
actually made by a self-assembled hexamer of one protein -- that is,
one gene produces one protein, and six copies of this (wedge-shaped)
protein form a ring (hexa = six). Since all six 'parts' are in fact
identical, there is really no crucial 'part' -- remove one of the
subunits of the ring, and the same gene can produce an identical
replacement. One part only, so no IC here:
In the simplest form of hexameric AAA assembly, the six
subunits are identical and monomodular (with a single AAA module per
polypeptide subunit), exemplified by the microtubule severing protein
katanin [35] and HslU [33], the six subunits are identical and each
contains a single AAA module that serves both the ATPase and the
structural/regulatory functions of the assembly through cooperative
interactions between modules that regulate the steps in their ATPase
cycle [42].
Here is Figure 3 from Ogura and Wilkinson (2001) showing some ribbon
models of AAA ATPase hexamers [note: no permission to reproduce as of
yet]:
However, other AAA ATPases are more complex. Some AAA ATPases are
coded for by six genes, arrayed next to each other along the
chromosome. Six copies of the gene can occur very simply by gene
duplication; what is interesting about this situation is that the
duplication allows each copy to evolve independently, and therefore to
specialize to perform nonuniform functions in the AAA ATPase ring.
Mocz and Gibbons (2001) note that:
Other AAA proteins form into more complex assemblies that
permit greater functional specialization of the individual AAA
modules. One such form, found in both the eukaryotic proteasome and
in dynein, has involved a six-fold replication of the gene encoding
the polypeptide subunits forming the hexameric assembly. This
replication permits the individual AAA modules to evolve separately
and acquire distinct structural and functional properties. In the 19S
regulating component of the eukaryotic proteasome, this
differentiation of AAA modules has progressed to the point that the
deletion of the gene encoding any one of the six is lethal, indicating
that the individual subunits, although closely related in sequence,
are functionally noninterchangeable [40].
If you blinked, you might have missed it: we just moved from non-IC to
IC using very simple, well understood genetic processes -- and we're
not even at dynein yet!
So where does dynein come in? Well, it turns out that the dynein heavy
In the simple AAA ATPase, all of the 6 subunits could hydrolyze ATP.
But interestingly, in dynein, one of the former genes (now a single
domain of the
six-domain dynein protein, labelled D1) has specialized to do the ATP
hydrolysis, and the other domains act to help transmit the resulting
mechanical energy to the power stroke of the stalk:
Concomitant with the development of its asymmetrical
structure, the dynein motor unit has evolved a functional dominance of
the D1 module, which alone has retained the full ability for binding
and hydrolysis of ATP [28]. Unlike the balanced extension of
differential function that appears to have occurred in the proteasome
regulator subunits during evolutionary passage from archaebacteria to
eukaryotes [39, 45], the other AAA modules in dynein heavy chains
appear to have progressively lost much of their typical AAA function
because they became fused into a single polypeptide. As discussed
above, modules D2, D3, and D4 appear to have lost their capability for
ATP hydrolysis, and the most degenerate modules, D5 and D6, show no
significant binding of ATP. The partial loss of active function in
five of its AAA modules not withstanding, the dynein motor appears to
require the presence of all its AAA modules for functional activity.
Expression constructs lacking any of the AAA modules, or even the
region of the tail component adjacent to D1 (residues 1400-1813),
appear to show no ATPase activity [11, 46]. This requirement for
structural integrity of the dynein motor unit resembles that of other
members of the oligomeric ATPase class and may indicate that
cooperative interactions of module D1 with the other AAA modules play
an essential role in transferring the energy made available at the
hydrolytic ATP binding site in D1 to the microtubule binding site
attached between D4 and D5.
A good electron micrograph (EM) of the DHC is found in Asai and Koonce
(2001). Here is Figure 1 from their article [note: no permission to
reproduce at
present]:
The "modified ring of repeated domains" is immediately obvious in
these micrographs.
Summary
Key:
Step 1: IDdidit.
The Evolution of Cilial (axoneme) Dynein from Cytoplasmic Dynein
If you check out these two papers:
Gibbons, I. R. (1995). "Dynein family of motor proteins: Present
status and future questions." Cell Motility and the Cytoskeleton,
32(2): 136-144. Link.
Asai, D. J. and Koonce, M. F. (2001). "The dynein heavy chain:
structure, mechanics and evolution." Trends in Cell Biology, V11(N5):
196-202. Link.
...you will discover, hopefully not to your surprise at this point,
that a similar process can be traced in the evolution of cilial dynein
from cytoplasmic dynein. To wit, cytoplasmic dynein usually occurs as
a homodimer (two identical subunits encoded by one gene):
Cytoplasmic dynein: dynein heavy chain gene --> dyneinHC-dyneinHC
...but, in cilial dynein, the DHCs appear as heterodimers or
heterotrimers (two or three distinct dynein heavy chains), e.g.:
Cilial dynein: DHC gene1, DHC gene1, --> DHC1-DHC2
...and there is even a subfamily of DHCs, DYH1B, that is
'transitional' in that it closer to cytoplasmic dyneins in sequence,
but has a cilial function more
similar to that of the cilial dyneins, indicating that the
cytoplasmic-->cilial transition may be happening again (discussed by
Gibbons 1995 and another article I don't have handy at the moment from
the same issue of Cell Motility and the Cytoskeleton, a special issue
on cellular motility that is yet another pre-1996 source that Behe
might have mentioned to his readers).
The Practical Results of Evolutionary Theory for Dynein Research
I can't resist giving you just one more bit. It is commonly argued by
ID supporters that evolution has little relevance or application to
fields outside of evolutionary biology. This is just plain false, and
is especially surprising coming from people who often talk like they
know a lot about biological
information and functional complexity. Bioinformatics, genomics and
protenomics rely fundamentally on the concepts of common descent and
homology,
which allow the crucial insight "if X is related to Y, then something
that we already know about X may help us in figuring out how Y works".
And exactly
this logic is used in the Mocz and Gibbons (2001) paper, X being AAA
ATPases, and Y being dynein. The exact mechanism by which ATP
hydrolysis results in mechanical energy is still undetermined. But
Mocz and Gibbons are able to use the evolutionary insight to propose a
functional model for dynein:
Biological Implications
This is an insight Mocz and Gibbon would have lost if they had been
satisfied with "IDdidit."
Endnotes
[1] Hoskin, Ned R. (1999) "A peek under the hood." Biofocus: A
research publication of the Wadsworth Center of and the Albany Medical
College.
Accessed online 1/2002. Link:
http://www.wadsworth.org/publish/biofocus/oct98/hood.htm. A slightly
dated article (pre-dating the homology work in 2000 and 2001) on
dynein research, this is a good brief intro to some of what is going
on in dynein research.
[2] See this course webpage on cellular motors at the University of
Leeds. Links and article references are extensive.
References
Behe, Michael J. (1996). Darwin’s black box : the biochemical
challenge to evolution. New York, Free Press, pp. xii, 307. Link.
Gibbons I. R. and Rowe A. (1965). "Dynein: a protein with adenosine
triphosphatase activity from cilia." Science, 149:424. Note: Gibbons
was one of the guys who discovered dynein 30+ years ago.
Neuwald A.F., Aravind L., Spouge J.L., Koonin E.V. (1999) "AAA+: A
class of chaperone-like ATPases associated with the assembly,
operation, and disassembly of protein complexes." Genome Res.
9(1):27-43. PubMed Link.
Nurminsky D.I., Nurminskaya M.V., De Aguiar D., Hartl D.L. (1998)
"Selective sweep of a newly evolved sperm-specific gene in
Drosophila." Nature. 396(6711):572-5. PubMed Link.
Nurminsky D., Aguiar D. D., Bustamante C.D., Hartl D.L. (2001)
"Chromosomal effects of rapid gene evolution in Drosophila
melanogaster." Science. 291(5501):128-30. PubMed Link.
Ogura T., Wilkinson A.J. (2001) "AAA+ superfamily ATPases: common
structure--diverse function." Genes Cells. 6(7):575-97. PubMed Link.
Vallee R. (1993). "Molecular analysis of the microtubule motor
dynein." Proc Natl Acad Sci U S A. 90(19):8769-72. Note: This
article is dated but gives a good overview of early molecular research
on dynein. Handily, it is also free online at PNAS.
Vallee R.B., Gee M.A. (1998). "Make room for dynein." Trends Cell
Biol. 8 (12):490-4. This article discusses how dynein is oriented
with and "packs" around microtubules. Pubmed link.
Koonce MP, Tikhonenko I. (2000). "Functional elements within the
dynein microtubule-binding domain." Mol Biol Cell. 11(2):523-9. Note:
Another freely available article on how dynein interacts with
microtubules.
Vorobjev I., Malikov V., Rodionov V. (2001). "Self-organization of a
radial microtubule array by dynein-dependent nucleation of
microtubules." Proc Natl Acad Sci U S A. 98(18):10160-5. An example
of a function for cytoplasmic dynein in assembling spindle-type
structures. Free at PNAS.
=======
Comments welcome,
Nic Tamzek
PS: Email me if you want the HTML as I have it up at a site for
private viewing (which some of you already know about).
Dunk
<snip>
>Hey, thanks for the comments. Actually, I've been inspired to expand
>a bit, heading towards a FAQ perhaps. See below.
Seconded.
>> (snip)
>>
>> Nick has my vote too. Now that we have established in another thread that
>> Behe probably has more research funding than the average evolutionary
>> biologist,
>
>Eh? Which thread was that?
My question too.
-------
Don't forget his other redefinition (arn site)
<quote>
Envisioning IC in terms of selected or unselected steps thus puts the
focus on the process of trying to build the system. A big advantage, I
think, is that it encourages people to pay attention to details;
hopefully it would encourage really detailed scenarios by proponents of
Darwinism (ones that might be checked experimentally) and discourage
just-so stories that leap over many steps without comment. So with those
thoughts in mind, I offer the following tentative “evolutionary”
definition of irreducible complexity:
An irreducibly complex evolutionary pathway is one that contains one or
more unselected steps (that is, one or more necessary-but-unselected
mutations). The degree of irreducible complexity is the number of
unselected steps in the pathway.
That definition has the advantage of promoting research: to state clear,
detailed evolutionary pathways; to measure probabilistic resources; to
estimate mutation rates; to determine if a given step is selected or not.
It allows for the proposal of any evolutionary scenario a Darwinist (or
others) may wish to submit, asking
only that it be detailed enough so that relevant parameters might be
estimated. If the improbability of the pathway exceeds the available
probabilistic resources (roughly the number of organisms over the
relevant time in the relevant phylogenetic branch) then Darwinism is
deemed an unlikely explanation and intelligent design a likely one.
<end quote>
http://www.arn.org/docs/behe/mb_indefenseofbloodclottingcascade.htm
and the 'necessarily' clause in the modified definition in Biology &
Philosophy paper. Also, at the end of that paper, he says now that his
argument is esentially based on [imagined] probability.
It must be getting too obvious that IC evolves.
>Here's the latest incarnation. In the HTML version I steal some pics
>from articles, but you'll have to use your imagination or look at the
>articles via PubMed...
I think you will be able to get permission to use the pictures.
Dunk
< giant snip>
zosdad
has most of the relevant papers in pdf form, freely available online:
http://mcb.berkeley.edu/courses/mcb290/pdf_Files/AAA_Motors/
...and this power-point presentation may make most of the points I was
trying to make, except via graphics:
http://mcb.berkeley.edu/courses/mcb290/pdf_Files/AAA_Motors/AAA_motors.ppt
Here's the course page, follow the links for pdfs on many different
motors that are the favorites of IDists...
http://mcb.berkeley.edu/courses/mcb290/
Nic Tamzek
beagle...@gmail.com
This is a l-o-n-g delayed reply to your post about the Chronicle's 2001 colloquy on "intelligent design." Not sure if you even still montior this site, but in case you do, I am trying to write a critical retrospective article on problems & contriductions within ID concepts over the years, and have been trying to find a transcript of that original colloquy in the Chronicle. The Chronicle's own search engine turns up nothing (!) except some of the last letters posted in response on Feb 1 2002. The links you posted in this page above no longer seem to work. I'm wondering: Any chance you archived the text of the original colloquy exchanges? I've already contacted Chronicle's editorial office & thus far they offer no help.
thanks, Don Beagle < beagle...@gmail.com > or < donald...@bac.edu >
Ron O
> On Saturday, January 19, 2002 9:40:08 AM UTC-5, Howard Hershey wrote:
>
> > Nick Tamzek wrote:
>
> Nick,
>
> This is a l-o-n-g delayed reply to your post about the Chronicle's 2001 colloquy on "intelligent design." Not sure if you even still montior this site, but in case you do, I am trying to write a critical retrospective article on problems & contriductions within ID concepts over the years, and have been trying to find a transcript of that original colloquy in the Chronicle. The Chronicle's own search engine turns up nothing (!) except some of the last letters posted in response on Feb 1 2002. The links you posted in this page above no longer seem to work. I'm wondering: Any chance you archived the text of the original colloquy exchanges? I've already contacted Chronicle's editorial office & thus far they offer no help.
>
> thanks, Don Beagle < beagle...@gmail.com > or < donald...@bac.edu >
The Colloquy discussion is a good example of why ID never amounted to anything. Several Discovery Institute ID perps put in their 2 cents, but as strange as it may seem none of them indicated that the Bait and Switch was planned to go down in Ohio (the reason for the discussion). The Discovery Institute was present in Ohio in force. According to news reports half a dozen IDiots (including Chapman) from the Discovery Institute came in addition to Meyer and Wells to the Ohio fiasco. It is pretty sad that instead of any ID to teach all the Ohio State board of education got from the ID perps was a switch scam that didn't even mention that ID ever existed. Ever since Ohio every IDiot that has wanted to teach the science of intelligent design has had the bait and switch run on them. Sad, but true. The Discovery Institute even tried to run the bait and switch on the Dover rubes, but the Dover IDiots had already obtained their "free" legal assistance and decided to try to teach the bogus ID junk. If the Disco
very Institute had gotten their way in Dover ID would probably have never had it's day in court.
What is even sadder is that after the IDiot dog and pony show the science side had been so convincing in their presentation demonstrating that ID was not science that there were members of the Ohio board that put one of the stupidest things anyone supposedly interested in education would do. They proposed changing the definition of science so that ID could be taught in the Ohio schools as science. The proposal was on the agenda for several months, but was never acted on that I know of.
Ohio was the end of any serious consideration of intelligent design because even the Discovery Institute ID perps gave up on it when it came time to put up or shut up. The ID perps obviously could have had Ohio teach ID anyway that they thought that it could be taught, but instead The ID perps ran the bait and switch and only gave the Ohio rubes a stupid switch scam that failed to mention anything about ID as any controversy worth teaching. No intelligent design science has ever been given to any IDiot rube that wanted to teach ID in the public schools. The bait and switch has been going on for over 10 years. ID is like some type of brainless zombie at this time. Just ask an IDiot like Kalk for the science of ID that never existed.
The Colloquy discussion was archived here:
http://web.archive.org/web/20021119135500/http://chronicle.com/colloquy/2001/design/re4.htm
Ron Okimoto
Chris Thompson
"Disco
very Institute".
I think I like Disco Institute as shorthand for that organization.
Chris
Ron O
>
>
> All I can say is that the GG line-wrap turned "Discovery Institute" into
>
> "Disco
>
> very Institute".
>
> I think I like Disco Institute as shorthand for that organization.
>
> Chris
The Designer works in mysterious ways. Just ask the guys at the Disco Tute.
Ron Okimoto
jillery
<the_th...@earthlink.net> wrote:
>All I can say is that the GG line-wrap turned "Discovery Institute" into
>"Disco
>very Institute".
>
>I think I like Disco Institute as shorthand for that organization.
Walter Bushell
> All I can say is that the GG line-wrap turned "Discovery Institute" into
> "Disco
> very Institute".
--
Never attribute to stupidity that which can be explained by greed. Me.
William Morse
compare Intelligent Design to Lee Trevino's (possibly apocryphal)
comment about why he held up a one iron while caught in a thunderstorm
on a golf course - "because not even God can hit a one iron"