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Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.

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.

SUBMITTER: Williams MJ

PROVIDER: S-EPMC7105384 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.

Williams Marc J MJ Zapata Luis L Werner Benjamin B Barnes Chris P CP Sottoriva Andrea A Graham Trevor A TA

eLife 20200330

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 ...[more]

PMID: 32223898

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