{"doi":"10.1126/science.abj7185","title":"Pleiotropic effects of trans-regulatory mutations on fitness and gene expression","abstract":"\n Variation in gene expression arises from cis- and trans-regulatory mutations, which contribute differentially to expression divergence. We compare the impacts on gene expression and fitness resulting from cis- and trans-regulatory mutations in\n Saccharomyces cerevisiae\n , with a focus on the\n TDH3\n gene. We use the effects of cis-regulatory mutations to infer effects of trans-regulatory mutations attributable to impacts beyond the focal gene, revealing a distribution of pleiotropic effects. Cis- and trans-regulatory mutations had different effects on gene expression with pleiotropic effects of trans-regulatory mutants affecting expression of genes both in parallel to and downstream of the focal gene. The more widespread and deleterious effects of trans-regulatory mutations we observed are consistent with their decreasing relative contribution to expression differences over evolutionary time.\n ","journal":"Science","year":2022,"id":22290,"datarank":1.2863383626986629,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":0.6747077461128047,"self_endowment_contribution":0.611630616585858,"citer_contribution":0.6747077461128047,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":50,"citers_with_citation_signal":31,"citers_with_endowment":31,"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":140623,"name":"Mark S. Hill","orcid":"0000-0003-0718-8934","position":1,"is_corresponding":false},{"id":136954,"name":"Patricia J. Wittkopp","orcid":"0000-0001-7619-0048","position":2,"is_corresponding":false},{"id":140622,"name":"Pétra Vande Zande","orcid":"0000-0002-4789-9899","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.07753744390572,"endowment":4.07753744390572,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35771906","pmcid":"PMC9569154","openalex_id":"https://openalex.org/W4283731821","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM089736","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM007544","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM108826","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM118073","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM108826-02","title":"Evolution of Gene Expression in Yeast"},{"funder_name":"National Institutes of Health","grant_id":"5T32GM007544-32","title":"Michigan Predoctoral Training Program in Genetics"},{"funder_name":"National Institutes of Health","grant_id":"5R35GM118073-09","title":"Genetic mechanisms and evolutionary processes underlying diversity within and between species"},{"funder_name":"National Institutes of Health","grant_id":"5R35GM118073-02","title":"Genetic mechanisms and evolutionary processes underlying diversity within and between species"}],"total_grants":8,"fwci":9.88,"citation_percentile":0.98578494,"influential_citations":2,"citation_trend":[{"year":2022,"count":4},{"year":2023,"count":22},{"year":2024,"count":13},{"year":2025,"count":14},{"year":2026,"count":5}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9569154","host_type":"repository"},{"url":"https://www.science.org/doi/pdf/10.1126/science.abj7185?download=true","host_type":"BRONZE"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9569154","host_type":"repository"},{"url":"https://www.science.org/doi/pdf/10.1126/science.abj7185","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.abj7185","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35771906","host_type":"repository"}],"fields_of_study":["Evolution and Genetic Dynamics","CRISPR and Genetic Engineering","Viral Infectious Diseases and Gene Expression in Insects","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Alleles","Evolution, Molecular","Gene Expression","Gene Expression Regulation, Fungal","Genetic Fitness","Genetic Variation","Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)","Mutation","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins"],"mesh_terms":["Alleles","Mutation","Saccharomyces cerevisiae","Genetic Variation","Gene Expression","Gene Expression Regulation, Fungal","Evolution, Molecular","Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)","Saccharomyces cerevisiae Proteins","Genetic Fitness"],"keywords":["Gene","Biology","Regulator gene","Genetics","Gene expression","Trans-acting","Regulatory sequence","Regulation of gene expression","Mutation","Saccharomyces cerevisiae","Mutant","Evolution, Molecular","Saccharomyces cerevisiae Proteins","Gene Expression Regulation, Fungal","Genetic Variation","Genetic Fitness","Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)","Alleles"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T18:34:48.200207Z","pmid":null,"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":[]}