{"doi":"10.7554/elife.48714","title":"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.","journal":"eLife","year":2020,"id":60743,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":235936,"name":"Luís Zapata","orcid":"0000-0002-1386-2019","position":1,"is_corresponding":false},{"id":264308,"name":"Benjamin Werner","orcid":"0000-0002-6857-8699","position":2,"is_corresponding":false},{"id":264311,"name":"C. Barnes","orcid":"0000-0002-9459-1395","position":3,"is_corresponding":false},{"id":264314,"name":"Andrea Sottoriva","orcid":"0000-0001-6709-9533","position":4,"is_corresponding":false},{"id":264313,"name":"Trevor A. Graham","orcid":"0000-0001-9582-1597","position":5,"is_corresponding":false},{"id":264306,"name":"Marc Williams","orcid":"0000-0001-5524-4174","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T21:09:05.493770Z","pmid":"32223898","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}