In mammals, it is usually assumed that selection cannot be strong enough to
act on nucleotide mutations that do not cause a change at the protein leve
l (i.e. 'silent' or 'synonymous' mutations). Here we report the results of
a molecular evolutionary analysis of BRCA1. We find a repeatable pronounced
peak in the ratio of nonsynonymous to synonymous substitutions between cod
ons 200-300. Unusually,this peak is caused by a plummet in the silent-site
rate of evolution. The most parsimonious interpretation of these data is th
at purifying selection is acting on silent sites.