Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements.
Background selection
Selective sweeps
demographic history
evolutionary biology
genetics
genomics
human
neutral diversity
positive selection
purifying selection
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 Jun 2023
23 Jun 2023
Historique:
received:
03
12
2021
accepted:
22
08
2022
medline:
26
6
2023
pubmed:
6
10
2022
entrez:
5
10
2022
Statut:
epublish
Résumé
Analyses of genetic variation in many taxa have established that neutral genetic diversity is shaped by natural selection at linked sites. Whether the mode of selection is primarily the fixation of strongly beneficial alleles (selective sweeps) or purifying selection on deleterious mutations (background selection) remains unknown, however. We address this question in humans by fitting a model of the joint effects of selective sweeps and background selection to autosomal polymorphism data from the 1000 Genomes Project. After controlling for variation in mutation rates along the genome, a model of background selection alone explains ~60% of the variance in diversity levels at the megabase scale. Adding the effects of selective sweeps driven by adaptive substitutions to the model does not improve the fit, and when both modes of selection are considered jointly, selective sweeps are estimated to have had little or no effect on linked neutral diversity. The regions under purifying selection are best predicted by phylogenetic conservation, with ~80% of the deleterious mutations affecting neutral diversity occurring in non-exonic regions. Thus, background selection is the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.
Identifiants
pubmed: 36196994
doi: 10.7554/eLife.76065
pii: 76065
pmc: PMC10299832
doi:
pii:
Banques de données
Dryad
['10.5061/dryad.n8pk0p2x0']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM115889
Pays : United States
Organisme : NIH HHS
ID : T32GM008798
Pays : United States
Organisme : NIH HHS
ID : GM115889
Pays : United States
Organisme : NIH HHS
ID : GM115889
Pays : United States
Organisme : NIH HHS
ID : T32GM008798
Pays : United States
Informations de copyright
© 2023, Murphy et al.
Déclaration de conflit d'intérêts
DM, GS No competing interests declared, EE is affiliated with MyHeritage. The author has no financial interests to declare, GA is affiliated with Flatiron Health Inc, The author has no financial interests to declare
Références
PLoS Genet. 2014 Jun 26;10(6):e1004434
pubmed: 24968283
Genet Res. 2001 Oct;78(2):149-61
pubmed: 11732092
Annu Rev Genomics Hum Genet. 2019 Aug 31;20:461-493
pubmed: 31283361
Genetics. 1995 Dec;141(4):1605-17
pubmed: 8601498
Genetics. 1997 Nov;147(3):1303-16
pubmed: 9383072
PLoS Genet. 2014 Mar 27;10(3):e1004222
pubmed: 24675740
Genetics. 2003 May;164(1):389-98
pubmed: 12750349
Theor Popul Biol. 2003 Aug;64(1):67-79
pubmed: 12804872
Genetics. 2015 Oct;201(2):707-25
pubmed: 26311475
Nature. 2017 Sep 28;549(7673):519-522
pubmed: 28959963
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Curr Opin Genet Dev. 2006 Dec;16(6):606-10
pubmed: 17027252
Nature. 2015 Oct 1;526(7571):75-81
pubmed: 26432246
Bioinformatics. 2006 May 1;22(9):1036-46
pubmed: 16500937
Science. 2012 Sep 28;337(6102):1675-8
pubmed: 22956687
Genetics. 2018 Aug;209(4):1235-1278
pubmed: 29844134
Genetics. 1931 Mar;16(2):97-159
pubmed: 17246615
PLoS Biol. 2018 Mar 16;16(3):e2002985
pubmed: 29547617
Genetics. 2000 Jun;155(2):909-19
pubmed: 10835409
Science. 2005 Oct 14;310(5746):321-4
pubmed: 16224025
Genetics. 2001 Dec;159(4):1805-17
pubmed: 11779816
Nature. 2014 Mar 20;507(7492):354-7
pubmed: 24476815
Elife. 2018 Aug 23;7:
pubmed: 30125248
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6815-8
pubmed: 8041702
Mol Biol Evol. 1993 Jul;10(4):842-54
pubmed: 8355603
PLoS Genet. 2009 Jan;5(1):e1000336
pubmed: 19148272
Genome Res. 2005 Aug;15(8):1034-50
pubmed: 16024819
Nat Rev Genet. 2010 Oct;11(10):665-7
pubmed: 20838407
Genome Res. 2008 Nov;18(11):1829-43
pubmed: 18849525
Genome Res. 2004 Apr;14(4):708-15
pubmed: 15060014
Annu Rev Genomics Hum Genet. 2009;10:285-311
pubmed: 19630562
Nat Genet. 2009 Apr;41(4):393-5
pubmed: 19287383
Nat Rev Genet. 2015 Jun;16(6):359-71
pubmed: 25963373
Genetics. 2012 Sep;192(1):205-24
pubmed: 22714413
Bioinformatics. 2016 Jan 15;32(2):283-5
pubmed: 26395773
Annu Rev Biochem. 2003;72:291-336
pubmed: 12626338
Genome Biol. 2017 Nov 13;18(1):215
pubmed: 29132403
Genetics. 2002 Jun;161(2):835-48
pubmed: 12072478
PLoS Biol. 2007 Nov 6;5(11):e310
pubmed: 17988176
Nature. 2014 Jan 2;505(7481):43-9
pubmed: 24352235
Genetics. 2020 Apr;214(4):1019-1030
pubmed: 32071195
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
pubmed: 14681465
Mol Biol Evol. 2002 Mar;19(3):336-40
pubmed: 11861892
Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1553-62
pubmed: 11127900
Nat Methods. 2020 Mar;17(3):261-272
pubmed: 32015543
Nature. 1992 Apr 9;356(6369):519-20
pubmed: 1560824
Philos Trans R Soc Lond B Biol Sci. 2017 Dec 19;372(1736):
pubmed: 29109230
Mol Ecol. 2018 Oct;27(19):3873-3888
pubmed: 29603507
Science. 2011 Feb 18;331(6019):920-4
pubmed: 21330547
Science. 2018 May 11;360(6389):656-660
pubmed: 29674434
Genetics. 2002 May;161(1):389-410
pubmed: 12019253
Science. 2019 Jan 25;363(6425):
pubmed: 30679340
Nature. 2020 Jul;583(7818):699-710
pubmed: 32728249
Genet Res. 1996 Apr;67(2):159-74
pubmed: 8801188
J Hered. 2013 Mar;104(2):161-71
pubmed: 23303522
PLoS Genet. 2016 Aug 18;12(8):e1006130
pubmed: 27536991
Mol Biol Evol. 2004 Mar;21(3):468-88
pubmed: 14660683
Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5
pubmed: 23193258
Philos Trans R Soc Lond B Biol Sci. 2010 Apr 27;365(1544):1245-53
pubmed: 20308100
PLoS Genet. 2009 May;5(5):e1000471
pubmed: 19424416
Genetics. 1964 Apr;49:725-38
pubmed: 14156929
Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6131-8
pubmed: 24753594
Sci Adv. 2020 Feb 12;6(7):eaax5097
pubmed: 32095519
Genetics. 2012 Nov;192(3):1065-93
pubmed: 22960212
Nature. 2010 Dec 23;468(7327):1053-60
pubmed: 21179161
J Math Biol. 2006 Nov;53(5):821-41
pubmed: 16960689
PLoS Biol. 2011 Jul;9(7):e1001091
pubmed: 21750661
Genetics. 2005 Apr;169(4):2335-52
pubmed: 15716498
Nature. 2011 Jul 20;476(7359):170-5
pubmed: 21775986
PLoS Genet. 2016 Nov 15;12(11):e1006315
pubmed: 27846220
Bioinformatics. 2011 Aug 1;27(15):2156-8
pubmed: 21653522
PLoS Genet. 2006 Jul;2(7):e105
pubmed: 16895447
Nat Rev Genet. 2003 Aug;4(8):587-97
pubmed: 12897771
Genetics. 2000 Jun;155(2):929-44
pubmed: 10835411
Genome Res. 2005 Jul;15(7):901-13
pubmed: 15965027
Nat Genet. 2014 Aug;46(8):919-25
pubmed: 24952747
PLoS Genet. 2018 Jun 18;14(6):e1007387
pubmed: 29912945
Nature. 2012 Aug 23;488(7412):471-5
pubmed: 22914163
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Nature. 2005 Aug 11;436(7052):876-80
pubmed: 15988478
Genet Res. 1966 Dec;8(3):269-94
pubmed: 5980116
Mol Biol Evol. 2006 May;23(5):1076-84
pubmed: 16520336
Genetics. 2016 Jun;203(2):881-91
pubmed: 27038113
Nat Genet. 2017 Feb;49(2):303-309
pubmed: 28024154
Am J Hum Genet. 2021 Apr 1;108(4):597-607
pubmed: 33675682
PLoS Biol. 2005 Jul;3(7):e196
pubmed: 15907155
Curr Biol. 2010 Feb 23;20(4):R208-15
pubmed: 20178769
Nature. 2007 Oct 18;449(7164):851-61
pubmed: 17943122
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
PLoS Genet. 2016 Nov 8;12(11):e1006340
pubmed: 27824859
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Genetics. 2019 Dec;213(4):1513-1530
pubmed: 31653678
Genetics. 2007 Dec;177(4):2083-99
pubmed: 18073425
PLoS Genet. 2009 Jun;5(6):e1000500
pubmed: 19503611
PLoS Genet. 2018 Sep 18;14(9):e1007641
pubmed: 30226838
Science. 2010 May 7;328(5979):710-722
pubmed: 20448178
Genome Res. 2007 Dec;17(12):1755-62
pubmed: 17989248
PLoS Genet. 2014 Jul 24;10(7):e1004525
pubmed: 25057982
Genetics. 1989 Dec;123(4):887-99
pubmed: 2612899
PLoS Genet. 2006 Dec 15;2(12):e186
pubmed: 17173482
Nat Commun. 2019 Oct 11;10(1):4630
pubmed: 31604926
Nat Commun. 2019 Aug 29;10(1):3900
pubmed: 31467277
Genetics. 1993 Aug;134(4):1289-303
pubmed: 8375663
Genetics. 2006 Nov;174(3):1421-30
pubmed: 16951057
Elife. 2022 Sep 26;11:
pubmed: 36155653
Genome Res. 2014 Jun;24(6):885-95
pubmed: 24619126
Science. 2014 Feb 28;343(6174):1017-21
pubmed: 24476670
Evolution. 2005 Nov;59(11):2312-23
pubmed: 16396172
Mol Biol Evol. 2009 Aug;26(8):1823-7
pubmed: 19420049
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9491-9500
pubmed: 31019089
Genet Res. 1974 Feb;23(1):23-35
pubmed: 4407212
Curr Biol. 2016 May 9;26(9):1241-7
pubmed: 27032491
PLoS Genet. 2009 Jun;5(6):e1000495
pubmed: 19503600
Nat Rev Genet. 2013 Apr;14(4):262-74
pubmed: 23478346