Evidence for purifying selection acting on silent sites in BRCA1

Trends Genet. 2001 Feb;17(2):62-5. doi: 10.1016/s0168-9525(00)02173-9.


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 level (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 codons 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 that purifying selection is acting on silent sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evolution, Molecular
  • Gene Silencing*
  • Genes, BRCA1*
  • Humans
  • Selection, Genetic*