{"doi":"10.1101/082297","title":"Striking differences in patterns of germline mutation between mice and humans","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Recent whole genome sequencing (WGS) studies have estimated that the human germline mutation rate per basepair per generation (∼1.2−10\n                  <jats:sup>−8</jats:sup>\n                  )\n                  <jats:sup>1,2</jats:sup>\n                  is substantially higher than in mice (3.5-5.4−10\n                  <jats:sup>−9</jats:sup>\n                  )\n                  <jats:sup>3,4</jats:sup>\n                  , which has been attributed to more efficient purifying selection due to larger effective population sizes in mice compared to humans.\n                  <jats:sup>5,6,7</jats:sup>\n                  . In humans, most germline mutations are paternal in origin and the numbers of mutations per offspring increase markedly with paternal age\n                  <jats:sup>2,8,9</jats:sup>\n                  and more weakly with maternal age\n                  <jats:sup>10</jats:sup>\n                  . Germline mutations can arise at any stage of the cellular lineage from zygote to gamete, resulting in mutations being represented in different proportion and types of cells, with the earliest embryonic mutations being mosaic in both somatic and germline cells. Here we use WGS of multi-sibling mouse and human pedigrees to show striking differences in germline mutation rate and spectra between the two species, including a dramatic reduction in mutation rate in human spermatogonial stem cell (SSC) divisions, which we hypothesise was driven by selection. The differences we observed between mice and humans result from both biological differences within the same stage of embryogenesis or gametogenesis and species-specific differences in cellular genealogies of the germline.\n                </jats:p>","journal":null,"year":null,"id":689327,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":133471,"name":"Raheleh Rahbari","orcid":"0000-0002-1839-7785","position":1,"is_corresponding":false},{"id":211198,"name":"Joanna Kaplanis","orcid":null,"position":2,"is_corresponding":false},{"id":15622,"name":"Thomas Keane","orcid":"0000-0001-7532-6898","position":3,"is_corresponding":false},{"id":18887,"name":"Matthew E. Hurles","orcid":"0000-0002-2333-7015","position":4,"is_corresponding":false},{"id":1800824,"name":"Sarah J. Lindsay","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Striking differences in patterns of germline mutation between mice and humans","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Recent whole genome sequencing (WGS) studies have estimated that the human germline mutation rate per basepair per generation (∼1.2−10\n                  <jats:sup>−8</jats:sup>\n                  )\n                  <jats:sup>1,2</jats:sup>\n                  is substantially higher than in mice (3.5-5.4−10\n                  <jats:sup>−9</jats:sup>\n                  )\n                  <jats:sup>3,4</jats:sup>\n                  , which has been attributed to more efficient purifying selection due to larger effective population sizes in mice compared to humans.\n                  <jats:sup>5,6,7</jats:sup>\n                  . In humans, most germline mutations are paternal in origin and the numbers of mutations per offspring increase markedly with paternal age\n                  <jats:sup>2,8,9</jats:sup>\n                  and more weakly with maternal age\n                  <jats:sup>10</jats:sup>\n                  . Germline mutations can arise at any stage of the cellular lineage from zygote to gamete, resulting in mutations being represented in different proportion and types of cells, with the earliest embryonic mutations being mosaic in both somatic and germline cells. Here we use WGS of multi-sibling mouse and human pedigrees to show striking differences in germline mutation rate and spectra between the two species, including a dramatic reduction in mutation rate in human spermatogonial stem cell (SSC) divisions, which we hypothesise was driven by selection. The differences we observed between mice and humans result from both biological differences within the same stage of embryogenesis or gametogenesis and species-specific differences in cellular genealogies of the germline.\n                </jats:p>","is_dataset_classified":null,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W2532471201","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"098051","title":"Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":7},{"year":2018,"count":4},{"year":2019,"count":2}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/05/23/082297.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/05/23/082297.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/082297","host_type":"publisher"},{"url":"https://doi.org/10.1101/082297","host_type":"repository"},{"url":"https://www.nature.com/articles/s41467-019-12023-w.pdf","host_type":""},{"url":"https://dx.doi.org/10.1101/082297","host_type":""},{"url":"http://dx.doi.org/10.1101/082297","host_type":""}],"fields_of_study":["Evolution and Genetic Dynamics","CRISPR and Genetic Engineering","Cancer Genomics and Diagnostics","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Germline","Biology","Germline mosaicism","Germline mutation","Mutation rate","Genetics","Zygote","Somatic cell","Mutation","Gamete","Mutation Accumulation","Population","Offspring","Gametogenesis","Embryo","Embryogenesis","Gene","Human fertilization"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-20T16:27:51.525895Z","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":[]}