{"doi":"10.1371/journal.pcbi.1005541","title":"High-order epistasis shapes evolutionary trajectories","abstract":null,"journal":"PLOS Computational Biology","year":2017,"id":46873,"datarank":4.480833131393804,"base_score":5.030437921392435,"endowment":5.030437921392435,"self_citation_contribution":0.7545656882088654,"citation_network_contribution":3.7262674431849385,"self_endowment_contribution":0.7545656882088654,"citer_contribution":3.7262674431849385,"corpus_percentile":null,"corpus_rank":null,"citation_count":152,"citer_count":149,"citers_with_citation_signal":124,"citers_with_endowment":124,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":216710,"name":"Michael J. Harms","orcid":"0000-0002-0241-4122","position":1,"is_corresponding":false},{"id":216709,"name":"Zachary R. Sailer","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"High-order epistasis shapes evolutionary trajectories","abstract":"High-order epistasis-where the effect of a mutation is determined by interactions with two or more other mutations-makes small, but detectable, contributions to genotype-fitness maps. While epistasis between pairs of mutations is known to be an important determinant of evolutionary trajectories, the evolutionary consequences of high-order epistasis remain poorly understood. To determine the effect of high-order epistasis on evolutionary trajectories, we computationally removed high-order epistasis from experimental genotype-fitness maps containing all binary combinations of five mutations. We then compared trajectories through maps both with and without high-order epistasis. We found that high-order epistasis strongly shapes the accessibility and probability of evolutionary trajectories. A closer analysis revealed that the magnitude of epistasis, not its order, predicts is effects on evolutionary trajectories. We further find that high-order epistasis makes it impossible to predict evolutionary trajectories from the individual and paired effects of mutations. We therefore conclude that high-order epistasis profoundly shapes evolutionary trajectories through genotype-fitness maps.","is_dataset_classified":null,"base_score":5.030437921392435,"endowment":5.030437921392435,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28505183","pmcid":"PMC5448810","openalex_id":"https://openalex.org/W2615678788","authors":[],"funders":[{"funder_name":"Alfred P. 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