Nature 449, 913-918 (18 October 2007) | doi:10.1038/nature06250; Received 8 August 2007; Accepted 13 September 2007

Genome-wide detection and characterization of positive selection in human populations

Pardis C. Sabeti1,79, Patrick Varilly1,79, Ben Fry1, Jason Lohmueller1, Elizabeth Hostetter1, Chris Cotsapas1,2, Xiaohui Xie1, Elizabeth H. Byrne1, Steven A. McCarroll1,2, Rachelle Gaudet3, Stephen F. Schaffner1, Eric S. Lander1,4,5,6 & The International HapMap Consortium

  1. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
  2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
  3. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
  4. Department of Biology, MIT, Cambridge, Massachusetts 02139, USA
  5. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
  6. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
  7. The Scripps Research Institute, 10550 North Torrey Pines Road MEM275, La Jolla, California 92037, USA.
  8. Perlegen Sciences, 2021 Stierlin Court, Mountain View, California 94043, USA.
  9. Baylor College of Medicine, Human Genome Sequencing Center, Department of Molecular and Human Genetics, 1 Baylor Plaza, Houston, Texas 77030, USA.
  10. Affymetrix, 3420 Central Expressway, Santa Clara, California 95051, USA.
  11. Pacific Biosciences, 1505 Adams Drive, Menlo Park, California 94025, USA.
  12. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
  13. The Broad Institute of Harvard and Massachusetts Institute of Technology, 1 Kendall Square, Cambridge, Massachusetts 02139, USA.
  14. Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 100300, China.
  15. Massachusetts General Hospital and Harvard Medical School, Simches Research Center, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
  16. Chinese National Human Genome Center at Beijing, 3-707 N. Yongchang Road, Beijing Economic-Technological Development Area, Beijing 100176, China.
  17. Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Shanghai 201203, China.
  18. Fudan University and CAS-MPG Partner Institute for Computational Biology, School of Life Sciences, SIBS, CAS, Shanghai, 201203, China.
  19. The Chinese University of Hong Kong, Department of Biochemistry, The Croucher Laboratory for Human Genetics, 6/F Mong Man Wai Building, Shatin, Hong Kong.
  20. Hong Kong University of Science and Technology, Department of Biochemistry and Applied Genomics Center, Clear Water Bay, Knowloon, Hong Kong.
  21. Illumina, 9885 Towne Centre Drive, San Diego, California 92121, USA.
  22. Complete Genomics, 658 North Pastoria Avenue, Sunnyvale, California 94085, USA.
  23. Prognosys Biosciences, 4215 Sorrento Valley Boulevard, Suite 105, San Diego, California 92121, USA.
  24. McGill University and Génome Québec Innovation Centre, 740 Dr Penfield Avenue, Montréal, Québec H3A 1A4, Canada.
  25. University of Montréal, The Public Law Research Centre (CRDP), PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
  26. Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Suite 500, Toronto, Ontario, M5G 1L7, Canada.
  27. University of California, San Francisco, Cardiovascular Research Institute, 513 Parnassus Avenue, Box 0793, San Francisco, California 94143, USA.
  28. Washington University School of Medicine, Department of Genetics, 660 S. Euclid Avenue, Box 8232, St Louis, Missouri 63110, USA.
  29. University of Hong Kong, Genome Research Centre, 6/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong.
  30. University of Tokyo, Institute of Medical Science, 4-6-1 Sirokanedai, Minatoku, Tokyo 108-8639, Japan.
  31. RIKEN SNP Research Center, 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama, Kanagawa 230-0045, Japan.
  32. Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  33. University of Cambridge, Department of Oncology, Cambridge CB1 8RN, UK.
  34. Solexa, Chesterford Research Park, Little Chesterford, nr Saffron Walden, Essex CB10 1XL, UK.
  35. Columbia University, 500 West 120th Street, New York, New York 10027, USA.
  36. University of Leicester, Department of Genetics, Leicester LE1 7RH, UK.
  37. Johns Hopkins University School of Medicine, McKusick-Nathans Institute of Genetic Medicine, Broadway Research Building, Suite 579, 733 N. Broadway, Baltimore, Maryland 21205, USA.
  38. University of Michigan, Center for Statistical Genetics, Department of Biostatistics, 1420 Washington Heights, Ann Arbor, Michigan 48109, USA.
  39. International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, Maryland 20850, USA.
  40. Center for Biomolecular Science and Engineering, Engineering 2, Suite 501, Mail Stop CBSE/ITI, UC Santa Cruz, Santa Cruz, California 95064, USA.
  41. University of Oxford, Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK.
  42. University of Chicago, Department of Statistics, 5734 S. University Avenue, Eckhart Hall, Room 126, Chicago, Illinois 60637, USA.
  43. Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
  44. University of Oxford/Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
  45. University of Washington Department of Biostatistics, Box 357232, Seattle, Washington 98195, USA.
  46. US National Institutes of Health, National Human Genome Research Institute, 50 South Drive, Bethesda, Maryland 20892, USA.
  47. US National Institutes of Health, National Library of Medicine, National Center for Biotechnology Information, 8600 Rockville Pike, Bethesda, Maryland 20894, USA.
  48. University of Chicago, Department of Medicine, Section of Genetic Medicine, 5801 South Ellis, Chicago, Illinois 60637, USA.
  49. Beijing Normal University, 19 Xinjiekouwai Street, Beijing 100875, China.
  50. Health Sciences University of Hokkaido, Ishikari Tobetsu Machi 1757, Hokkaido 061-0293, Japan.
  51. Shinshu University School of Medicine, Department of Medical Genetics, Matsumoto 390-8621, Japan.
  52. United Nations Educational, Scientific and Cultural Organization (UNESCO Bangkok), 920 Sukhumwit Road, Prakanong, Bangkok 10110, Thailand.
  53. University of Tsukuba, Eubios Ethics Institute, PO Box 125, Tsukuba Science City 305-8691, Japan.
  54. Howard University, National Human Genome Center, 2216 6th Street, NW, Washington, District of Columbia 20059, USA.
  55. University of Ibadan College of Medicine, Ibadan, Oyo State, Nigeria.
  56. Case Western Reserve University School of Medicine, Department of Bioethics, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
  57. University of Utah, Eccles Institute of Human Genetics, Department of Human Genetics, 15 North 2030 East, Salt Lake City, Utah 84112, USA.
  58. Chinese Academy of Social Sciences, Institute of Philosophy/Center for Applied Ethics, 2121, Building 9, Caoqiao Xinyuan 3 Qu, Beijing 100067, China.
  59. Genetic Interest Group, 4D Leroy House, 436 Essex Road, London N130P, UK.
  60. Kyoto University, Institute for Research in Humanities and Graduate School of Biostudies, Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.
  61. Nagasaki University Graduate School of Biomedical Sciences, Department of Human Genetics, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.
  62. University of Oklahoma, Department of Anthropology, 455 W. Lindsey Street, Norman, Oklahoma 73019, USA.
  63. Vanderbilt University, Center for Genetics and Health Policy, 507 Light Hall, Nashville, Tennessee 37232, USA.
  64. Wellcome Trust, 215 Euston Road, London NW1 2BE, UK.
  65. Washington University School of Medicine, Genome Sequencing Center, Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA.
  66. Chinese Academy of Sciences, 52 Sanlihe Road, Beijing 100864, China.
  67. Genome Canada, 150 Metcalfe Street, Suite 2100, Ottawa, Ontario K2P 1P1, Canada.
  68. McGill University, Office of Technology Transfer, 3550 University Street, Montréal, Québec H3A 2A7, Canada.
  69. Génome Québec, 630, boulevard René-Lévesque Ouest, Montréal, Québec H3B 1S6, Canada.
  70. Ministry of Education, Culture, Sports, Science, and Technology, 3-2-2 Kasumigaseki, Chiyodaku, Tokyo 100-8959, Japan.
  71. Ministry of Science and Technology of the People's Republic of China, 15 B. Fuxing Road, Beijing 100862, China.
  72. The Human Genetic Resource Administration of China, b7, Zaojunmiao, Haidian District, Beijing 100081, China.
  73. US National Institutes of Health, National Human Genome Research Institute, 5635 Fishers Lane, Bethesda, Maryland 20892, USA.
  74. US National Institutes of Health, Office of Behavioral and Social Science Research, 31 Center Drive, Bethesda, Maryland 20892, USA.
  75. Novartis Pharmaceuticals Corporation, Biomarker Development, One Health Plaza, East Hanover, New Jersey 07936, USA.
  76. US National Institutes of Health, Office of Technology Transfer, 6011 Executive Boulevard, Rockville, Maryland 20852, USA.
  77. University of Maryland School of Law, 500 W. Baltimore Street, Baltimore, Maryland 21201, USA.
  78. US National Institutes of Health, National Human Genome Research Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
  79. These authors contributed equally to this work.
  80. Lists of participants and affiliations appear at the end of the paper.

Correspondence to: Correspondence and requests for materials should be addressed to P.C.S. (Email: pardis@broad.mit.edu).

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2)1. We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection2, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus3, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation4, 5, in Europe; and EDAR and EDA2R, both involved in development of hair follicles6, in Asia.


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