Evolution and Protein Folds
robison1 at husc10.harvard.edu
Sun Jun 26 22:20:55 EST 1994
ram at mbisgi.umd.edu (Ram Samudrala) writes:
>Simon Brocklehurst (Bioc) (smb18 at mole.bio.cam.ac.uk) wrote:
>> What you wrote is generally accepted as being correct. Quite a lot
>>is known about what kind of amino acid substitutions are acceptable in
>>particular structural environments.
>I am now confused as to what you mean by "acceptable". Who decides
>what is acceptable? Remember, there's no selection on the protein
>produced by the gene yet. What's to prevent it from mutating a
>residue in the hydrophobic core to an ASP and thereby destabilising
>the fold by a few Cal? Given that there's no selection on this
>protein, it doesn't seem to matter if it folds up or not. But it
>does, if it has to evolve to a new function. Thus there is some
>mechanism that makes sure a compact-fold is preserved.
I think you have answered your own question. If a protein has the
potential to be functional only if it is folded correctly, than any
genes which have structure-disrupting mutations in them must either
be compensated for by other mutations (or back mutations) or they
are doomed to become pseudogenes.
>What is the mechanism that ensures that no mutations that destroy the
>fold (again, there's really no protein deficiency) are not selected
To reiterate, there is no need to invoke a special mechanism.
Genes unable to provide a usable structure are unavailable for
further selection; genes which fortuitiously retain a useable
structural framework can acquire new, selectable functions.
Department of Cellular and Developmental Biology
Department of Genetics / HHMI
krobison at nucleus.harvard.edu
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