title: Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing.
abstract: We study genome-wide nucleotide diversity in three subspecies of extant chimpanzees using exome capture. After strict filtering, Single Nucleotide Polymorphisms and indels were called and genotyped for greater than 50% of exons at a mean coverage of 35× per individual. Central chimpanzees (Pan troglodytes troglodytes) are the most polymorphic (nucleotide diversity, θw = 0.0023 per site) followed by Eastern (P. t. schweinfurthii) chimpanzees (θw = 0.0016) and Western (P. t. verus) chimpanzees (θw = 0.0008). A demographic scenario of divergence without gene flow fits the patterns of autosomal synonymous nucleotide diversity well except for a signal of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked versus autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection statistic exhibits a strong nonmonotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous versus nonsynonymous frequency classes to infer the distribution of S coefficients acting on nonsynonymous mutations in each subspecies. The strength of purifying selection we infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human populations.
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bataillon
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Duan
authors.affiliation: Science and Conservation, Copenhagen Zoo, Denmark Bioinformatics, University of Copenhagen, Denmark tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Christina
authors.initials: C
authors.lastname: Hvilsom
authors.affiliation: BGI Shenzhen, China tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: BGI Shenzhen, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark.
authors.forename: Laurits
authors.initials: L
authors.lastname: Skov
authors.affiliation: Institut des Sciences de l'Evolution, Universite Montpellier 2, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Glemin
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Munch
authors.affiliation: BGI Shenzhen, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Hobolth
authors.affiliation: BGI Shenzhen, China Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark The Department of Genetic Medicine, Faculty of Medicine and Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia Department of Biology, University of Copenhagen, Denmark Macau University of Science and Technology, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mailund
authors.affiliation: Bioinformatics, University of Copenhagen, Denmark tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Siegismund
authors.affiliation: Bioinformatics Research Centre, Aarhus University, Denmark tbata@birc.au.dk hsiegismund@bio.ku.dk mheide@birc.au.dk.
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Schierup
mesh_terms: D000818:Animals; D003710:Demography; D059472:Exome; D005091:Exons; D056084:Genetic Fitness; D023281:Genomics; D006801:Humans; D054643:INDEL Mutation; D002679:Pan troglodytes / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
keywords: effective size; fitness effect; mutation; selection
references.citation: Ann N Y Acad Sci. 2014 Jul;1320:76-92
references.pmid: 24891070
references.citation: PLoS Genet. 2013 Oct;9(10):e1003905
references.pmid: 24204310
references.citation: Genetics. 2000 Sep;156(1):385-99
references.pmid: 10978302
references.citation: Mol Biol Evol. 2004 May;21(5):799-808
references.pmid: 14963091
references.citation: Mol Biol Evol. 2005 Feb;22(2):297-307
references.pmid: 15483319
references.citation: Genetics. 2006 Jun;173(2):891-900
references.pmid: 16547091
references.citation: PLoS Genet. 2007 Apr 20;3(4):e66
references.pmid: 17447846
references.citation: Genetics. 2007 Dec;177(4):2251-61
references.pmid: 18073430
references.citation: Trends Genet. 2014 Apr;30(4):133-9
references.pmid: 24656563
references.citation: Science. 2014 Jun 13;344(6189):1272-5
references.pmid: 24926018
references.citation: PLoS Genet. 2008 Apr;4(4):e1000057
references.pmid: 18421364
references.citation: PLoS Genet. 2008 May;4(5):e1000083
references.pmid: 18516229
references.citation: J Mol Evol. 2008 Oct;67(4):418-26
references.pmid: 18818860
references.citation: Mol Biol Evol. 2009 Sep;26(9):2097-108
references.pmid: 19535738
references.citation: Mol Biol Evol. 2010 Apr;27(4):921-33
references.pmid: 19955478
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Apr 27;365(1544):1187-93
references.pmid: 20308093
references.citation: Mol Biol Evol. 2010 Jun;27(6):1425-35
references.pmid: 20118191
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Oct 27;365(1556):3277-88
references.pmid: 20855302
references.citation: Mol Biol Evol. 2011 Jan;28(1):63-70
references.pmid: 20837603
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4766-71
references.pmid: 21368170
references.citation: Mol Biol Evol. 2011 Aug;28(8):2239-52
references.pmid: 21325092
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2054-9
references.pmid: 22308321
references.citation: Nature. 2012 Nov 1;491(7422):56-65
references.pmid: 23128226
references.citation: Genetics. 2013 Apr;193(4):1197-208
references.pmid: 23341416
references.citation: Heredity (Edinb). 2013 Jun;110(6):586-93
references.pmid: 23531981
references.citation: Mol Ecol. 2013 Jul;22(13):3525-38
references.pmid: 23773281
references.citation: Nature. 2013 Jul 25;499(7459):471-5
references.pmid: 23823723
references.citation: Primates. 2014 Jan;55(1):101-12
references.pmid: 23982179