Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32223898.
- Also identified by DOI 10.7554/eLife.48714 and PMC identifier 7105384.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in somatic cells. However the link, in somatic evolution, between dN/dS values and fitness coefficients is missing. Here we present a quantitative model of somatic evolutionary dynamics that determines the selective coefficients of individual driver mutations from dN/dS estimates. We then measure the DFE for somatic mutant clones in ostensibly normal oesophagus and skin. We reveal a broad distribution of fitness effects, with the largest fitness increases found for TP53 and NOTCH1 mutants (proliferative bias 1-5%). This study provides the theoretical link between dN/dS values and selective coefficients in somatic evolution, and measures the DFE of mutations in human tissues.
Medical subject headings
- Clonal Evolution
- Evolution, Molecular
- Genetic Fitness
- Mutation