ram at mbisgi.umd.edu (Ram Samudrala) writes:
Subject:Evolution and Protein Folds
Date: 24 Jun 1994 11:22:54 GMT
>Suppose we have a gene duplication. One copy of the gene stays
>mutationally put as there is selective pressure for the protein it
>produces. The other copy is free to accumulate mutations and perhaps
>evolve to a new function.
>Now, all the books I've read talk about evolution in terms of protein
>function. That is, there is selection as soon as the mutation gene
>produces a protein that has some function. What I am interested in
>knowing is if there is any model that speaks of evolution in terms of
>protein structure.
>I am interested in knowing this because I find it hard to believe that
>/any/ mutation will be tolerated in the gene while it is drifting and
>there's no selection for function. I believe that only
>genes/mutations that conserve the protein fold would be selected for.
[stuff deleted]
I've long been of the impresssion that the model:
duplicate -> drift awhile -> stumble into new function
was simplistic and unrealistic. My own prejudice is that the duplication
only persists if the resulting change in expression level is beneficial
and selection on both copies for the original function is maintained.
The stage is then set for specialization in both expression and the
actual function of the 2 proteins by the usual gradual and continuous
evolutionary process. I would suspect that in a complex multitissue
organism like the human, the problem of getting the correct expression
in each cell type dominates the early changes after duplication, and
that functional specialization of the protein sequences themselves
tends to set in later.
Having said that, you can imagine that 2 x expression after duplication
isn't necessarily the best outcome, and that the first mutational hit
drops one of the copies down to something like 10% efficiency where the
system stabilizes (if 1.1 x function is better than 1.0 x function).
Then the unmutated copy is destined to continue bearing the major brunt
of the function and stays under selection as before. The mutated copy
might now encounter increased plasticity because it doesn't have to work
very well; but it can't go away either. This scenario would block the
progression to pseudogene (which I would think would be very rapid
without some residual function) but still predispose to 'discovery'
of altered function.
Finally you can imagine some kind of 'mothball' selection after duplication
where one copy doesn't have to function, but some structural selection is
maintained because interaction of structurally damaged protein with other
cellular components is deleterious. Human delta globin is the best case
I know of for this (speculative) model. I understand that people with
deletions of delta have no deleterious phenotype, so the gene isn't required
(I'm not sure about delta thalasemia; there was some talk about people with
this in Japan, but I don't know if it was ever published).
But there is a selection (although reduced I think) against amino acid
replacements in the recent history of delta. So (thinking about
Sickle Cell) maybe making gummed up delta is still bad, even if no delta
is OK.
Steve Hardies Hardies at thorin.uthscsa.edu
