title: Global diversity, population stratification, and selection of human copy-number variation.
abstract: In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sudmant
authors.affiliation: Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Swapan
authors.initials: S
authors.lastname: Mallick
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Nelson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Hormozdiari
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Niklas
authors.initials: N
authors.lastname: Krumm
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: John
authors.initials: J
authors.lastname: Huddleston
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Coe
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Baker
authors.affiliation: Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nordenfelt
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98119, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Novosibirsk State University, Novosibirsk 630090, Russia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Posukh
authors.affiliation: Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
authors.forename: Hovhannes
authors.initials: H
authors.lastname: Sahakyan
authors.affiliation: Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: W Scott
authors.initials: WS
authors.lastname: Watkins
authors.affiliation: Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
authors.forename: Levon
authors.initials: L
authors.lastname: Yepiskoposyan
authors.affiliation: Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan, Brunei Darussalam.
authors.forename: M Syafiq
authors.initials: MS
authors.lastname: Abdullah
authors.affiliation: Laboratorio de Genética Molecular Poblacional, Instituto Multidisciplinario de Biología Celular (IMBICE), Centro Científico y Tecnológico-Consejo Nacional de Investigaciones Científicas y Técnicas (CCT-CONICET) and Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CICPBA), La Plata B1906APO, Argentina.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Bravi
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Cristian
authors.initials: C
authors.lastname: Capelli
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
authors.forename: Tor
authors.initials: T
authors.lastname: Hervig
authors.affiliation: National Cancer Centre Singapore, Singapore.
authors.forename: Joseph T S
authors.initials: JT
authors.lastname: Wee
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.affiliation: Institute of Linguistics, University of Bern, Bern CH-3012, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: van Driem
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Irene Gallego
authors.initials: IG
authors.lastname: Romero
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aashish R
authors.initials: AR
authors.lastname: Jha
authors.affiliation: Department of Medical Genetics, National Human Genome Center, Medical University Sofia, Sofia 1431, Bulgaria.
authors.forename: Sena
authors.initials: S
authors.lastname: Karachanak-Yankova
authors.affiliation: Department of Medical Genetics, National Human Genome Center, Medical University Sofia, Sofia 1431, Bulgaria.
authors.forename: Draga
authors.initials: D
authors.lastname: Toncheva
authors.affiliation: Institut de Biologia Evolutiva [Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra (CSIC-UPF)], Departament de Ciències Experimentals i de la Salut, UPF, Barcelona 08003, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Comas
authors.affiliation: Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Brenna
authors.initials: B
authors.lastname: Henn
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Fitzwilliam Street, Cambridge CB2 1QH, UK.
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, WC1E 6BT, UK.
authors.forename: Andres
authors.initials: A
authors.lastname: Ruiz-Linares
authors.affiliation: University of Helsinki, Department of Forensic Medicine, Helsinki 00014, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.affiliation: Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. University of Tartu, Department of Evolutionary Biology, Tartu 5101, Estonia.
authors.forename: Ene
authors.initials: E
authors.lastname: Metspalu
authors.affiliation: Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia.
authors.forename: Jüri
authors.initials: J
authors.lastname: Parik
authors.affiliation: Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia.
authors.forename: Richard
authors.initials: R
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authors.affiliation: Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Starikovskaya
authors.affiliation: Center for Global Health and Child Development, Kisumu 40100, Kenya.
authors.forename: George
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authors.lastname: Ayodo
authors.affiliation: Department of Anthropology, Case Western Reserve University, Cleveland, OH 44106-7125, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Beall
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Rienzo
authors.affiliation: Arizona Research Laboratories Division of Biotechnology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hammer
authors.affiliation: Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences, Ufa 450054, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa 450074, Russia.
authors.forename: Rita
authors.initials: R
authors.lastname: Khusainova
authors.affiliation: Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences, Ufa 450054, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa 450074, Russia.
authors.forename: Elza
authors.initials: E
authors.lastname: Khusnutdinova
authors.affiliation: Integrative Biology, University of California, Berkeley, CA 94720-3140, USA.
authors.forename: William
authors.initials: W
authors.lastname: Klitz
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Incorporated, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Winkler
authors.affiliation: Centre Hospitalier Universitaire (CHU) Sainte-Justine, Département de Pédiatrie, Université de Montréal, QC H3T 1C5, Canada.
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
authors.affiliation: Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia.
authors.forename: Mait
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authors.affiliation: Departments of Biology and Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Tishkoff
authors.affiliation: Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Department of Paleolithic Archaeology, Institute of Archaeology and Ethnography, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Dryomov
authors.affiliation: Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Altai State University, Barnaul 656000, Russia.
authors.forename: Rem
authors.initials: R
authors.lastname: Sukernik
authors.affiliation: Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.affiliation: Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. eee@gs.washington.edu.
authors.forename: Evan E
authors.initials: EE
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mesh_terms: D000818:Animals; D044383:Black People / Q000145:classification / Q000235:genetics; D056915:DNA Copy Number Variations; D019143:Evolution, Molecular; D020440:Gene Duplication; D015894:Genome, Human / Q000235:genetics*; D015186:Hominidae / Q000235:genetics; D006801:Humans; D044468:Native Hawaiian or Pacific Islander / Q000145:classification / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011153:Population / Q000235:genetics*; D012641:Selection, Genetic; D017384:Sequence Deletion