Williams, MJ;
Zapata, L;
Werner, B;
Barnes, CP;
Sottoriva, A;
Graham, TA;
(2020)
Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
Elife
, 9
, Article e48714. 10.7554/eLife.48714.
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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.
| Type: | Article |
|---|---|
| Title: | Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios. |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.48714 |
| Publisher version: | https://doi.org/10.7554/eLife.48714 |
| Language: | English |
| Additional information: | © Copyright Williams et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | Computational and systems biology, genetics and genomics, somatic evolution, cancer evolution, dn/ds, population genetics, distribution of fitness effects |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10094676 |
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