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Trends Genet. 2001 Feb;17(2):62-5.

Evidence for purifying selection acting on silent sites in BRCA1.

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Department of Biology and Biochemistry, University of Bath, Claverton Down, BA27AY, Bath, UK.


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.

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