Evidence for purifying selection acting on silent sites in BRCA1

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.