title: A time transect of exomes from a Native American population before and after European contact.
abstract: A major factor for the population decline of Native Americans after European contact has been attributed to infectious disease susceptibility. To investigate whether a pre-existing genetic component contributed to this phenomenon, here we analyse 50 exomes of a continuous population from the Northwest Coast of North America, dating from before and after European contact. We model the population collapse after European contact, inferring a 57% reduction in effective population size. We also identify signatures of positive selection on immune-related genes in the ancient but not the modern group, with the strongest signal deriving from the human leucocyte antigen (HLA) gene HLA-DQA1. The modern individuals show a marked frequency decrease in the same alleles, likely due to the environmental change associated with European colonization, whereby negative selection may have acted on the same gene after contact. The evident shift in selection pressures correlates to the regional European-borne epidemics of the 1800s.
authors.affiliation: Department of Human Genetics, University of Chicago, 920 E 58th Street, Chicago, Illinois 60637, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lindo
authors.affiliation: Department of Molecular Cell Biology, University of California, 5200 North Lake Road, Merced, California 95343, USA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sánchez
authors.affiliation: Department of Human Genetics, University of Chicago, 920 E 58th Street, Chicago, Illinois 60637, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakagome
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.|Department of Genetics, School of Medicine, Stanford University, 291 Campus Drive, Stanford, California 94305, USA.
authors.forename: Morten
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Metlakatla Treaty Office, PO Box 224, Prince Rupert, British Columbia V8J 3P6, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Petzelt
authors.affiliation: Metlakatla Treaty Office, PO Box 224, Prince Rupert, British Columbia V8J 3P6, Canada.
authors.forename: Joycelynn
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Canadian Museum of History, 100 Rue Laurier, Gatineau, Quebec K1A 0M8, Canada.|Department of Anthropology, University of Western Ontario, London, Ontario N6A 3K7, Canada.|Department of Archaeology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Cybulski
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.|Department of Zoology, University of Cambridge, Downing St., Cambridge CB2 3EJ, UK.|Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge Cb10 1SA, UK.
authors.forename: Eske
authors.initials: E
authors.lastname: Willerslev
authors.affiliation: Departments of Biology and Statistics, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA.|Institute for CyberScience, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: DeGiorgio
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois, 1206 W Gregory Dr., Urbana, Illinois 61820, USA.|Department of Anthropology, University of Illinois, 607 S. Mathews Ave., Urbana, Illinois 61820, USA.
authors.forename: Ripan S
authors.initials: RS
authors.lastname: Malhi
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods*; D005843:Geography; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008957:Models, Genetic; D009656:North America; D020641:Polymorphism, Single Nucleotide; D011157:Population Dynamics; D012641:Selection, Genetic; D044465:White People / Q000235:genetics*
chemical_list: D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen