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Evolution and Protein Folds

Ram Samudrala ram at mbisgi.umd.edu
Fri Jul 1 09:00:09 EST 1994

Regarding this thread, which I originally began, I would like to thank

robison1 at husc10.harvard.edu (Keith Robison)
schwarze at starbase1.caltech.edu (Erich Schwarz)
smb18 at mole.bio.cam.ac.uk (Simon Brocklehurst (Bioc))
cjamison at news.cso.uiuc.edu (Curt Jamison)
"Warren Gallin" <wgallin at gpu.srv.ualberta.ca>

who responded to my queries.  If I've forgotten someone, I apologise.
I would summarise, but I am still unclear and I seem to have gotten
more confused after all of this.  I do notice people touching the
point I was trying to make initially.  And so I will retstate my query

Dan Weinreich (dmw at MCZ.HARVARD.EDU) wrote:

>What would be needed are arguments of the form, "There hasn't been enough
>time since the origin of life for blind enzymatic stumbling to have
>produced the diversity seen," and I don't believe such an argument can be
>forcefully motivated.  So you're left simply saying, "On aesthetic
>grounds, I don't find it plausable that there's been enough time for blind
>enzymatic stumbling..."  It's legitimate to feel that way, but in and of
>itself, it ain't science.

I think if you assume a naive model, then one can say "random
mutations" cannot lead to new protien functions within the relevant
timescale.  Of course, we know mutations aren't completely random, and
so that might have something to do with it, but the problem I have
with evolution (which has led to a debate on sci.bio) is that this
mechanism is largely untestable.

This is why I initially asked if there was any model that talked about
evolution in terms of protein structure.  I didn't want to read about
the probability of a function being selected, but I wanted models that
would describe the probability of a function/structure arising in the
first place!  Even if you use the random mutation mechanism, there
must be a mathematical model (more complicated than a naive one),
right?  This is what I am trying to find.  Because with the discovery
of genes which produce misfolded proteins, we now have intermediates
in the picture of gene duplication -> drift -> new function.  We have
a gene in the drift stage and we can see if the mutations in the gene
would've occured if a random mutation model is the right answer.

(This is why I was looking for gene families also---as a way of
finding intermediates.)

In any case, I think believing evolution of new function is due to
"random mutations" is also not science.  And if I am wrong about this,
I would like to know, but as I understand it there is nothing that
models the mechanism of how mutations occur.  We do not know because
we have only snapshots of the beginning and the end.


ram at elan1.carb.nist.gov             Let's not judge outselves by race,
 religion, colour, or by sex. Let's reach out to one another bring out
  our very best.  We believe in what we're sayin' so put your trust in
     us.  We express ourselves by playin', we're called Psychefunkapus.

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