{"doi":"10.1101/2025.04.05.647371","title":"Low-dimensional genotype-fitness mapping across divergent environments suggests a limiting functions model of fitness","abstract":"A central goal in evolutionary biology is to be able to predict the effect of a genetic mutation on fitness. This is a major challenge because fitness depends both on phenotypic changes due to the mutation, and how these phenotypes map onto fitness in a particular environment. Genotype, phenotype, and environment spaces are extremely large and complex, rendering bottom-up prediction difficult. Here we show, using a large collection of adaptive yeast mutants, that fitness across a set of lab environments can be well-captured by low-dimensional linear models of abstract genotype-phenotype-fitness maps. We find that these maps are low-dimensional not only in the environment where the adaptive mutants evolved, but also in divergent environments. We further find that the genotype-phenotype-fitness spaces implied by these maps overlap only partially across environments. We argue that these patterns are consistent with a \"limiting functions\" model of fitness, whereby only a small number of limiting functions can be modified to affect fitness in any given environment. The pleiotropic side-effects on non-limiting functions are effectively hidden from natural selection locally, but can be revealed globally. These results combine to emphasize the importance of environmental context in genotype-phenotype-fitness mapping, and have implications for the predictability and trajectory of evolution in complex environments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555147,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":264406,"name":"Grant Kinsler","orcid":"0000-0001-8308-4665","position":1,"is_corresponding":false},{"id":563476,"name":"Benjamin H. Good","orcid":"0000-0002-7757-3347","position":2,"is_corresponding":false},{"id":264408,"name":"Dmitri A. Petrov","orcid":"0000-0002-3664-9130","position":3,"is_corresponding":false},{"id":1453440,"name":"Olivia M. Ghosh","orcid":"0000-0003-4149-840X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:59.329539Z","pmid":"40291729","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":[]}