In article <andrew.rambaut-ya023380001306971245430001 at news.ox.ac.uk>,
Andrew Rambaut <andrew.rambaut at zoology.ox.ac.uk> wrote:
>In article <5nmp30$ooh at ruacad.runet.edu>, rkliman at runet.edu (Richard M
>Kliman) wrote:
>>> >Many mutations in protein coding DNA do not result in a change in amino
>> >acid due to the redundancy of code. Thus these occur despite natural
>> >selection as there is no phenotype to be selected.
>>>> This is not always true. There is considerable evidence for selection
>> acting on silent substitutions, probably favoring those that increase the
>> efficiency and/or fidelity of translation.
>>The fact that many substitutions do not result in AA changes IS true. Some
>of these may be select for or against due to tendancies related to G/C bias
>etc. However it seems reasonably to say that most will simply be neutral -
>i.e. they had no affect on phenotype and were fixed by drift. Indeed is
>seems likely that many AA replacement substitutions will also be between
>AAs that have a minimal effect on the protein structure (i.e. changes tend
>to be withing AA groupings with respect to size and hydrophobicity).
Agreed, sort of. There is a difference between neutral in an
evolutionary sense and neutral in a phenotypic sense. Silent
substitutions *do* seem to be subject to selection in many
microorganisms, C. elegans and Drosophila. However, being subject to
selection (i.e., having a phenotypic effect) and being predictably
influenced by selection are two different things.
Take the case of Drosophila. Let's assume 20,000 protein-coding genes,
each with 500 codons on average - i.e., 10,000,000 codons in all. A
silent substitution at any site may have a very small phenotypic effect;
thus, for any given site, a betting person would expect an optimal codon
to be used. However, mutational biases, selection on linked sites, etc.
will also influence the history of a given silent mutation. We would
never expect optimal codon usage for all sites. Nonselective influences,
genetic drift and, possibly, other forms of selection on codon
usage/base composition are important.
Take-home message: for a variety of reasons, silent substitutions may
often be effectively neutral, in the sense that one can not reject a
neutral model. However, that does not make them truly neutral - i.e.,
they do not have a selection coefficient of zero. I think there is
considerable evidence for effective selection on silent mutations, and
one should be careful about assuming neutrality.
And, of course, a molecular clock does not assume selective neutrality.
I was simply trying to clear up a potentially misleading statement
regarding the selective neutrality of silent mutations.
Rich Kliman
