Brian Foley raises some interesting points, here are some possible ideas
in answer to his hypothesis:
Hypothesis 1: It is probably true that silent sites in the third position
are not truely silent, hence the idea of codon preference! Although,
structural requirements may necessitate the change in the third codon
from the "most common" base in some cases.
Hypothesis 2: It is also true that introns "mutate" faster than exons,
because mutations within the codon region i.e exons that are deliterious
to the organism are most likely to be selected against-i.e the organism dies
and we do not sample the change!. Especially if the mutations are in a gene of
functional importance. The histone genes are very conserved between species,
and I imagine would not tolerate mutation because they are of extreme
Mutations within introns would be less deliterious because these are not
as functionaly important as exons (except perhaps the 5' and 3' ends),
hence would not be deliterious to the organism. I don't think the polymerase
differentiates between exon and intron, although this would be an interesting
hypothesis to test.
One could examine the replication of a defined piece of exon compared to an
intron within an in vitro system (for example construct YACS with bits of
exons and introns). One could introduce mutations within each region and see
if the polymerase preferentialy corrects/repairs exon DNA over intron DNA.
However, I think mutations within the exon are selected against either by
no translation of the protein or the protein that is produced is defective
and the organism cannot reproduce to pass on this change to the next
Julian A Hiscox.
E-mail: HISCOX at AFRC.AC.UK