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Updated: Oct 9, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
Published on: February 28, 2021
Evidence for purifying selection acting on silent sites in BRCA1
1Department of Biology and Biochemistry, University of Bath, Claverton Down, BA27AY, Bath, UK. l.d.hurst@bath.ac.uk
Abstract:
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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