{"doi":"10.1101/gr.219956.116","title":"Deep sequencing of natural and experimental populations of\n                    <i>Drosophila melanogaster</i>\n                    reveals biases in the spectrum of new mutations","abstract":"<jats:p>\n                    Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely rare polymorphisms from natural populations. The first, mutation accumulation (MA) lines are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. The second, rare genetic variation from natural populations allows the study of mutation because extremely rare polymorphisms are relatively unaffected by the filter of natural selection. We use both methods in\n                    <jats:italic>Drosophila melanogaster</jats:italic>\n                    , first generating our own novel data set of sequenced MA lines and performing a meta-analysis of all published MA mutations (∼2000 events) and then identifying a high quality set of ∼70,000 extremely rare (≤0.1%) polymorphisms that are fully validated with resequencing. We use these data sets to precisely measure mutational rates and patterns. Highlights of our results include: a high rate of multinucleotide mutation events at both short (∼5 bp) and long (∼1 kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and using our precise context-dependent mutation rates to predict long-term evolutionary patterns at synonymous sites. We also show that de novo mutations from independent MA experiments display similar patterns of single nucleotide mutation and well match the patterns of mutation found in natural populations.\n                  </jats:p>","journal":"Genome Research","year":2017,"id":608477,"datarank":0.6010999777848708,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":0.0,"self_endowment_contribution":0.6010999777848708,"citer_contribution":0.0,"corpus_percentile":67.1,"corpus_rank":4329,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"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":566175,"name":"Susanne Tilk","orcid":"0000-0002-9156-9360","position":1,"is_corresponding":false},{"id":86640,"name":"Jane Park","orcid":"0000-0003-1935-4514","position":2,"is_corresponding":false},{"id":331912,"name":"Mark L. Siegal","orcid":"0000-0001-6930-2988","position":3,"is_corresponding":false},{"id":264408,"name":"Dmitri A. Petrov","orcid":"0000-0002-3664-9130","position":4,"is_corresponding":false},{"id":1562824,"name":"Zoe June Assaf","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Deep sequencing of natural and experimental populations of\n                    <i>Drosophila melanogaster</i>\n                    reveals biases in the spectrum of new mutations","abstract":"<jats:p>\n                    Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely rare polymorphisms from natural populations. The first, mutation accumulation (MA) lines are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. The second, rare genetic variation from natural populations allows the study of mutation because extremely rare polymorphisms are relatively unaffected by the filter of natural selection. We use both methods in\n                    <jats:italic>Drosophila melanogaster</jats:italic>\n                    , first generating our own novel data set of sequenced MA lines and performing a meta-analysis of all published MA mutations (∼2000 events) and then identifying a high quality set of ∼70,000 extremely rare (≤0.1%) polymorphisms that are fully validated with resequencing. We use these data sets to precisely measure mutational rates and patterns. Highlights of our results include: a high rate of multinucleotide mutation events at both short (∼5 bp) and long (∼1 kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and using our precise context-dependent mutation rates to predict long-term evolutionary patterns at synonymous sites. We also show that de novo mutations from independent MA experiments display similar patterns of single nucleotide mutation and well match the patterns of mutation found in natural populations.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.007333185232471,"endowment":4.007333185232471,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29079675","pmcid":"PMC5741049","openalex_id":"https://openalex.org/W2952401095","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R01GM100366","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"T32 HG000044","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM118170","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM118165","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM100366-03","title":"Adaptation in 6 dimensions"}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":5},{"year":2019,"count":8},{"year":2020,"count":7},{"year":2021,"count":11},{"year":2022,"count":7},{"year":2023,"count":9},{"year":2024,"count":3},{"year":2025,"count":3}],"oa_status":"bronze","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"http://genome.cshlp.org/content/27/12/1988.full.pdf","host_type":"journal"},{"url":"http://genome.cshlp.org/content/27/12/1988.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gr.219956.116","host_type":"publisher"},{"url":"https://doi.org/10.1101/gr.219956.116","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29079675","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5741049","host_type":"repository"},{"url":"http://genome.cshlp.org/cgi/content/short/27/12/1988","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5741049","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5741049?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/095182","host_type":""},{"url":"http://dx.doi.org/10.1101/gr.219956.116","host_type":""},{"url":"https://dx.doi.org/10.1101/gr.219956.116","host_type":""},{"url":"https://dx.doi.org/10.1101/095182","host_type":""},{"url":"http://dx.doi.org/10.1101/095182","host_type":""}],"fields_of_study":["Evolution and Genetic Dynamics","Genomics and Phylogenetic Studies","RNA and protein synthesis mechanisms","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Base Composition","Base Pairing","Bias","Drosophila melanogaster","Female","High-Throughput Nucleotide Sequencing","Male","Mutation","Mutation Rate","Point Mutation","Polymorphism, Genetic"],"mesh_terms":["Animals","Base Composition","Drosophila melanogaster","Female","Male","Mutation","Polymorphism, Genetic","Bias","Point Mutation","Base Pairing","High-Throughput Nucleotide Sequencing","Mutation Rate"],"keywords":["Biology","Mutation rate","Genetics","Mutation","Mutation Accumulation","Natural selection","Drosophila melanogaster","Context (archaeology)","Population","Evolutionary biology","Gene","Male","Base Composition","Polymorphism, Genetic","Research","High-Throughput Nucleotide Sequencing","Bias","Animals","Point Mutation","Female","Base Pairing"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"No poverty"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T16:43:48.440608Z","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":[]}