{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:23:44Z","timestamp":1782854624691,"version":"3.54.5"},"reference-count":69,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,5,13]]},"abstract":"<jats:p>How the genetic composition of a population changes through stochastic processes, such as genetic drift, in combination with deterministic processes, such as selection, is critical to understanding how phenotypes vary in space and time. Here, we show how evolutionary forces affecting selection, including recombination and effective population size, drive genomic patterns of allele-specific expression (ASE). Integrating tissue-specific genotypic and transcriptomic data from 1500 individuals from two different cohorts, we demonstrate that ASE is less often observed in regions of low recombination, and loci in high or normal recombination regions are more efficient at using ASE to underexpress harmful mutations. By tracking genetic ancestry, we discriminate between ASE variability due to past demographic effects, including subsequent bottlenecks, versus local environment. We observe that ASE is not randomly distributed along the genome and that population parameters influencing the efficacy of natural selection alter ASE levels genome wide.<\/jats:p>","DOI":"10.1126\/sciadv.abl3819","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T17:57:20Z","timestamp":1652464640000},"source":"Crossref","is-referenced-by-count":12,"title":["Recombination affects allele-specific expression of deleterious variants in human populations"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-3373","authenticated-orcid":true,"given":"Michelle P.","family":"Harwood","sequence":"first","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-5479","authenticated-orcid":true,"given":"Isabel","family":"Alves","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Nantes, CHU Nantes, CNRS, INSERM, L\u2019Institut du thorax, F-44000 Nantes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-8349","authenticated-orcid":true,"given":"Hilary","family":"Edgington","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Wooster, Wooster, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-5299","authenticated-orcid":true,"given":"Mawusse","family":"Agbessi","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8058-8999","authenticated-orcid":true,"given":"Vanessa","family":"Bruat","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1325-7417","authenticated-orcid":true,"given":"David","family":"Soave","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."},{"name":"Department of Mathematics, Wilfrid Laurier University, Waterloo, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-7548","authenticated-orcid":true,"given":"Fabien C.","family":"Lamaze","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."},{"name":"Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-7584","authenticated-orcid":true,"given":"Marie-Julie","family":"Fav\u00e9","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9946-6393","authenticated-orcid":true,"given":"Philip","family":"Awadalla","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research, Toronto, ON, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2815"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv074"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159397"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055261"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12824"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0508-z"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79990-9"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.184"},{"key":"e_1_3_3_10_2","first-page":"649","article-title":"Gene expression levels are a target of recent natural selection in the human genome","volume":"3","author":"Kudaravalli S.","year":"2009","unstructured":"S. Kudaravalli, J. B. Veyrieras, B. E. Stranger, E. T. Dermitzakis, J. K. Pritchard, Gene expression levels are a target of recent natural selection in the human genome. Mol. Genet. Evol. 3, 649\u2013658 (2009).","journal-title":"Mol. Genet. Evol."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.495"},{"key":"e_1_3_3_12_2","first-page":"228","article-title":"Exploiting gene expression variation to capture gene-environment interactions for disease","volume":"3","author":"Idaghdour I.","year":"2012","unstructured":"I. Idaghdour, P. Awadalla, Exploiting gene expression variation to capture gene-environment interactions for disease. Front. Genet. 3, 228 (2012).","journal-title":"Front. Genet."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys160"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03202-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008749"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3216"},{"key":"e_1_3_3_17_2","first-page":"e1004260","article-title":"Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans","volume":"10","author":"Casals F.","year":"2013","unstructured":"F. Casals, A. Hodgkinson, J. Hussin, Y. Idaghdour, V. Bruat, T. Millard, J. C. Grenier, E. Gbeha, F. F. Hamdan, S. Girard, J. F. Spinella, M. Larivier, V. Saillour, P. Awadalla, Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans. PLOS Genet. 10, e1004260 (2013).","journal-title":"PLOS Genet."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300551"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0192-y"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301833"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300033619"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a004039"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.07.065"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05049"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.109.112920"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(64)90047-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300010156"},{"key":"e_1_3_3_28_2","first-page":"1239","article-title":"Reduced natural selection associated with low recombination in Drosophila melanogaster","volume":"10","author":"Kliman R. M.","year":"1993","unstructured":"R. M. Kliman, J. Hey, Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol. Biol. Evol. 10, 1239\u20131258 (1993).","journal-title":"Mol. Biol. Evol."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300034662"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672399003900"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6801059"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251110"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02122-z"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3582"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00570"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06258"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020148"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a003886"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1113"},{"key":"e_1_3_3_42_2","unstructured":"V. A. McKusick Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders (Johns Hopkins Univ. Press ed. 12 1998) vol. 4 pp. 588\u2013604."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000944"},{"key":"e_1_3_3_44_2","doi-asserted-by":"crossref","unstructured":"R. A. Fisher The Genetical Theory of Natural Selection (Clarendon Press Oxford 1930).","DOI":"10.5962\/bhl.title.27468"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0945-x"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10231"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/61.3.763"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510805112"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6023607"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3015"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.119636.110"},{"key":"e_1_3_3_52_2","first-page":"1.30.1","article-title":"The GeneCards Suite: From gene data mining to disease genome sequence analyses","volume":"54","author":"Stelzer G.","year":"2016","unstructured":"G. Stelzer, N. Rosen, I. Plaschkes, S. Zimmerman, M. Twik, S. Fishilevich, T. I. Stein, R. Nudel, I. Lieder, Y. Mazor, S. Kaplan, D. Dahary, D. Warshawsky, Y. Guan-Golan, A. Kohn, N. Rappaport, M. Safran, D. Lancet, The GeneCards Suite: From gene data mining to disease genome sequence analyses. Bioinformatics 54, 1.30.1\u20131.30.33 (2016).","journal-title":"Bioinformatics"},{"key":"e_1_3_3_53_2","first-page":"186","article-title":"Epigenetics and evolution","volume":"7","author":"Waddington C. H.","year":"1953","unstructured":"C. H. Waddington, Epigenetics and evolution. Symp. Soc. Exp. Biol 7, 186\u2013199 (1953).","journal-title":"Symp. Soc. Exp. Biol"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005665"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24277"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0579-4"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.052"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507611102"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000500"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-00304-w"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt958"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002453"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08250"},{"key":"e_1_3_3_65_2","first-page":"1","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates D.","year":"2014","unstructured":"D. Bates, M. Machler, B. Bolker, S. Walker, Fitting linear mixed-effects models using lme4. J. Stat. Softw. 67, 1\u201348 (2014).","journal-title":"J. Stat. Softw."},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts163"},{"key":"e_1_3_3_67_2","first-page":"5","article-title":"Improved whole-chromosome phasing for disease and population genetics studies","volume":"10","author":"Delaneau O.","year":"2013","unstructured":"O. Delaneau, J. F. Zagury, J. Marchini, Improved whole-chromosome phasing for disease and population genetics studies. Nat. Med. 10, 5\u20136 (2013).","journal-title":"Nat. Med."},{"key":"e_1_3_3_68_2","unstructured":"R Core Development Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing Vienna 2021); https:\/\/www.R-project.org\/."},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00772"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abl3819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T19:51:55Z","timestamp":1704829915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abl3819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,13]]},"references-count":69,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,5,13]]}},"alternative-id":["10.1126\/sciadv.abl3819"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abl3819","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,13]]},"article-number":"eabl3819"}}