and that this clinal structure of EA populations 15. 5. Xu, W. Huang, J. Qian, L Jin, Am. I. Hum. Genet. 82, Singapore. "institute of Medical Biology, Chinese/ arose from prehistoric population divergence rather 883008) ce, Kunming, China. l than IBD or gene flow from CSA populations. 16.S.Xu, WJin, L Jin, MoL. BioL. Evol. 26, 2197(2009). National Institutes of Health, University of the Philippines Manila, On the basis of increased cultural, linguistic 17. L. Reid, i 25 Pedro Gil Street, Ermita Manila 1000, Philippines. Cen Information Biology and DNA Data Bank of Japan, National and genetic diversity, the origins of sEA popula- ruyter, Berlin, 1994)pp. 443-475 Institute of Genetics, Research Organization of Information and origins of those to their north. Notably, the Negritos 19. 1. Y Chu et al, roc. Nat. Acad. Sci. U.S.A 95, 11763 medicinal Information Research Cente, as40, Japan. "io- tions are thought to be more complex than the 18. Indian Genome Variation Consortium, GEnet. of the Philippines and Malaysia differ from 20. B su et al. Am. 1. Hum. Genet. 65. 1718(1999). ku, Tokyo 135-0064, Japan." National Engineering Center for neighboring populations in aspects of their phys- 21. Y. C. Ding et al, Proc. Natl. Acod. Sci. U.S.A 97, 14003 Biochip, at Shanghai, 151 Li Bing ical appearance, prompting intense speculation about models of human settlement in Southeast 22. A Manica, F. Prugnolle, F. Balloux, Hum.Genet. 118 niversiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Asia. The two-wave hypothesis, which suggests 23. M.P. elle..A. Diniz-Filho. Genet Mol Res. 4. 742 (2005). Genomics, Chinese National Human northerly migration originating in or near the Mid on,N1993) and Molecular Medicine, Tokai University School of Medicine, dle East, and spreading both toward Europe and 25. L. L Cavalli-Sforza, M W Feldman, Nat. Genet 33.26 i state Key d cont 143 Shimokasuya, lsehara-A Kanagawa-Pref A259-1193, Japar gineering and MOE Northeast Asia via Central Asia (25), has been sup- 26.GH ported by phylogenetic trees constructed from data Auton, D. Alush. PLos Genet. 4 e100007802008) on a limited number of protein markers(24, 25). 27. The entire consortium thanks all individuals wh The topology of our population trees, both with olunteered their DNA for this project. It is this and without the data from additional European collaboration between scientists and the public that is and Asian populations discussed in(1), is in- sential to progress in our field. All SNP data have been submitted to dbsNP with the submission handle pasni consistent with regard to this genetic similarity and will become accessible in dbsNP Build 131. See SoM of European and EA populations( Figs. I and text for a complete listing of all acknowledgments Francisco, CA 94080, USA.The Centre for Genomic Appli 3D). Instead, on the basis of variation at a large okhla Industrial Estate. New Delhi 110020. India. "500 mber of independent SNPs, we observed that The HUGO Pan-Asian SNP Consortium there is substantial genetic proximity of SEA and Mahmood Ameen Abdulla, , khlak Ahme chai university, Sangdo-5-dong 1-1, Dongjak-gu, Seoul 156-743 ulji University College of Medicine, 143-5 Yong-du- ong Bhak, Samir K EA populations(fig. S28). An identical pattern is Gayelline C. CalacaL, Amit Chaurasia, Chien-h dong Jung-gu, Dae-jeon City 301-832, Korea 2Department of uman Genetics, Graduate School of Medicine, University of on all of their 642.690 SNPS. Our forward-time Cultiongco-de la Paz o Maria Corazon A. De unga. logeny is not the result of ascertainment bias. Jinan gun Jung, Daorong Kangwanp stitute, DSO National Laboratories, 27 Medical Drive, 117510 levels of migration between populations after Hyung-lae ng iai gIulia C. Kennes'san Simulation studies also suggest that substantial Jatupod Kampuansa Singapore. Indian Statistical Institute(Kolkata)203 Barrad their initial separation are unlikely to distort the Yeon kim,. Kuchan Kimm, Ryosuke Kimura, Tomohiro opology of the phylogeny(SOM text). opolis Way, 03-01 Nanos, 138669, Singapore. Division of To unambiguously infer popul ulation histories Partha P Majumder, an Kumar Mandapat dences, School of Computer Engineering, Nanyang represents a considerable challenge(26). Although Marzuki, "Wayne Mitchell 3 Mitali Mukerji, Kenji Naritomi," Technological University, 50 Nanyang Avenue, 639798, Singa this study does not disprove a two-wave model of Chumpol Ngamphiw Norio ikawa Nao Nishida, Bermseok pore. Department of Medical Genetics, University of the and the accompanying simulation studies (figs. perdigon Maulde elvira phip p sa einen png roshi ik: opment Agena. I hal Soience and Technology Devel- S29 and S30)point toward a history that unites the Negrito and non-Negrito populations of Southeast Scaria, Mark Seielstad, t Mohd Ros Sidek, Amit Sinha, Selatan, 46150 Bandar Sunway, Selangor, Malaysia. RIKEN and East Asia via a single primary wave of entry of humans into the continent. Adrian Tan, Katsushi Tokunaga, Sissades Tongsima, Lilian P. istry, University of Hong Kong, 3/F Laboratory Block, Faculty of uam Wu, Huasheng Xiao, Shuhua Laboratory of Functional Genomics, Department of Medical in Yas shugart - Sook Yoo, Wer Genome Sciences graduate School of Frontier Sciences. Univer- References and notes 1. J.Z. Li et al. Science 319, 11 inato-ku, Tokyo 108-8639, Japan.Chinese Academy of 2. M. Kayser et al, Am. ).Hum. 194(2008) rtment of Molecular Medicine, Faculty of Medicine, Saiences-Max Planck Society Partner Institute for Computa- 3. N. A Rosenberg et al. Plos and the Department of Anthropology, Faculty of Arts and tional Biology, Shanghai Institutes of Biological Sciences, chi- 81(2002) Social Sciences, University of Malaya, Kuala Lumpur, 50603, nese Academy of Sciences, 320 Yueyang Rd, Shanghai 200031, 5.. Novembre et al., Nature 456, 98(2008). M. Nelis et al. PLos One 4, e5472(2009) Council for scientific and industrial Mall Road. Delhi tal Health, National Institutes of Health, 6001 Exeautive Bou- C Tian ef al. PLos Genet. 4. e4(2008) 10007,India. Mahidol University, Salaya Campus, 25/25 levar, Bethesda, MD 20892 USA. Research Institute of 8.0. Lao et al,dur.Bi.18.1241(2008) M3, Puttamonthon 4 Road, Puttamonthon, Nakornpathom Personalized Health Sciences, Health Sciences University of 9. The International HapMap Consortium, Nature 426, 789 73170, Thailand. Biostatistics and Informatics Laboratory, Hokaido, Tobetsu 061-0293, Japan. 10. ).K Pritchard, M. Stephens, P. Donnelly, Genetics 155. e Institute, National Center for Genetic Engwani 12120, upporting Online Material 945(2000) d.koreanbIoinformationCenter(kobio,KoreaRe-www.sciencemag.org/cgi/content/full/326/5959/1541/dc1 11. H Tang, ).Peng, P. Wang, N ]. Risch, Genet. Epidemiol. search Institute of Bioscience and Biotechnology (KRIBB), 111 Materials and Methods Gwahangno, Yuseong-gu, Deajeon 305-806, Korea. DNA Anal SoM 12.]. L. Mountain, L. L. Cavalli-Sforza, Am. ). Hum. Genet. Laboratory, Natural Sciences Research Institute, University Figs. S1 to $38 61,705(1997) opines, Diliman, Quezon City 1101, Philippin 13. N. Patterson, A. L Price. D. Reich. PLos Genet. 2. e190 nstitute of Biomedical Sciences. Academia Sinica. 128 Sec 2 Academia Road Nangang, Taipei City 115, Taiwan. Genome 1 June 2009: accepted 13 October 2009 14. 5. Xu, L Jin, Am. /. Hum. Genet. 83, 322(2008 nstitute of Singapore, 60 Biopolis Street 02-01 138672, 10 1126/science. 1177074 www.sciencemag.orgScieNceVol32611DecembEr2009 1545and that this clinal structure of EA populations arose from prehistoric population divergence rather than IBD or gene flow from CSA populations. On the basis of increased cultural, linguistic, and genetic diversity, the origins of SEA popula￾tions are thought to be more complex than the origins of those to their north. Notably, the Negritos of the Philippines and Malaysia differ from neighboring populations in aspects of their phys￾ical appearance, prompting intense speculation about models of human settlement in Southeast Asia. The two-wave hypothesis, which suggests that ancestral Negrito populations settled in South￾east Asia, Australia, and Oceania before a more northerly migration originating in or near the Mid￾dle East, and spreading both toward Europe and Northeast Asia via Central Asia (25), has been sup￾ported by phylogenetic trees constructed from data on a limited number of protein markers (24, 25). The topology of our population trees, both with and without the data from additional European and Asian populations discussed in (1), is in￾consistent with regard to this genetic similarity of European and EA populations (Figs. 1 and 3D). Instead, on the basis of variation at a large number of independent SNPs, we observed that there is substantial genetic proximity of SEA and EA populations (fig. S28). An identical pattern is seen in the population tree of Li et al. (1) based on all of their 642,690 SNPs. Our forward-time simulation results under extreme ascertainment scenarios (SOM text) show that the observed phy￾logeny is not the result of ascertainment bias. Simulation studies also suggest that substantial levels of migration between populations after their initial separation are unlikely to distort the topology of the phylogeny (SOM text). To unambiguously infer population histories represents a considerable challenge (26). Although this study does not disprove a two-wave model of migration, the evidence from our autosomal data and the accompanying simulation studies (figs. S29 and S30) point toward a history that unites the Negrito and non-Negrito populations of Southeast and East Asia via a single primary wave of entry of humans into the continent. References and Notes 1. J. Z. Li et al., Science 319, 1100 (2008). 2. M. Kayser et al., Am. J. Hum. Genet. 82, 194 (2008). 3. N. A. Rosenberg et al., PLoS Genet. 1, e70 (2005). 4. N. A. Rosenberg et al., Science 298, 2381 (2002). 5. J. Novembre et al., Nature 456, 98 (2008). 6. M. Nelis et al., PLoS One 4, e5472 (2009). 7. C. Tian et al., PLoS Genet. 4, e4 (2008). 8. O. Lao et al., Curr. Biol. 18, 1241 (2008). 9. The International HapMap Consortium, Nature 426, 789 (2003). 10. J. K. Pritchard, M. Stephens, P. Donnelly, Genetics 155, 945 (2000). 11. H. Tang, J. Peng, P. Wang, N. J. Risch, Genet. Epidemiol. 28, 289 (2005). 12. J. L. Mountain, L. L. Cavalli-Sforza, Am. J. Hum. Genet. 61, 705 (1997). 13. N. Patterson, A. L. Price, D. Reich, PLoS Genet. 2, e190 (2006). 14. S. Xu, L. Jin, Am. J. Hum. Genet. 83, 322 (2008). 15. S. Xu, W. Huang, J. Qian, L. Jin, Am. J. Hum. Genet. 82, 883 (2008). 16. S. Xu, W. Jin, L. Jin, Mol. Biol. Evol. 26, 2197 (2009). 17. L. Reid, in Language Contact and Change in the Austronesian World. T. Dutton, T. Tryon, Eds. (Mouton de Gruyter, Berlin, 1994) pp. 443–475. 18. Indian Genome Variation Consortium, J. Genet. 87, 3 (2008). 19. J. Y. Chu et al., Proc. Natl. Acad. Sci. U.S.A. 95, 11763 (1998). 20. B. Su et al., Am. J. Hum. Genet. 65, 1718 (1999). 21. Y. C. Ding et al., Proc. Natl. Acad. Sci. U.S.A. 97, 14003 (2000). 22. A. Manica, F. Prugnolle, F. Balloux, Hum. Genet. 118, 366 (2005). 23. M. P. Telles, J. A. Diniz-Filho, Genet. Mol. Res. 4, 742 (2005). 24. L. L. Cavalli-Sforza, P. Menozzi, A. Piazza, The History and Geography of Human Genes (Princeton Univ. Press, Princeton, NJ, 1993). 25. L. L. Cavalli-Sforza, M. W. Feldman, Nat. Genet. 33, 266 (2003). 26. G. Hellenthal, A. Auton, D. Falush, PLoS Genet. 4, e1000078 (2008). 27. The entire consortium thanks all individuals who volunteered their DNA for this project. It is this collaboration between scientists and the public that is essential to progress in our field. All SNP data have been submitted to dbSNP with the submission handle PASNPI and will become accessible in dbSNP Build 131. See SOM text for a complete listing of all acknowledgments. The HUGO Pan-Asian SNP Consortium Mahmood Ameen Abdulla,1 Ikhlak Ahmed,2 Anunchai Assawamakin,3,4 Jong Bhak,5 Samir K. Brahmachari,2 Gayvelline C. Calacal,6 Amit Chaurasia,2 Chien-Hsiun Chen,7 Jieming Chen,8 Yuan-Tsong Chen,7 Jiayou Chu,9 Eva Maria C. Cutiongco-de la Paz,10Maria Corazon A. De Ungria,6 Frederick C. Delfin,6 Juli Edo,1 Suthat Fuchareon,3 Ho Ghang,5 Takashi Gojobori,11,12 Junsong Han,13 Sheng-Feng Ho,7 Boon Peng Hoh,14 Wei Huang,15 Hidetoshi Inoko,16 Pankaj Jha,2 Timothy A. Jinam,1 Li Jin,17,38† Jongsun Jung,18 Daoroong Kangwanpong,19 Jatupol Kampuansai,19 Giulia C. Kennedy,20,21 Preeti Khurana,22 Hyung-Lae Kim,18 Kwangjoong Kim,18 Sangsoo Kim,23 Woo￾Yeon Kim,5 Kuchan Kimm,24 Ryosuke Kimura,25 Tomohiro Koike,11 Supasak Kulawonganunchai,4 Vikrant Kumar,8 Poh San Lai,26,27 Jong-Young Lee,18 Sunghoon Lee,5 Edison T. Liu,8 † Partha P. Majumder,28 Kiran Kumar Mandapati,22 Sangkot Marzuki,29 Wayne Mitchell,30,31Mitali Mukerji,2 Kenji Naritomi,32 Chumpol Ngamphiw,4Norio Niikawa,40Nao Nishida,25 Bermseok Oh,18 Sangho Oh,5 Jun Ohashi,25 Akira Oka,16 Rick Ong,8 Carmencita D. Padilla,10 Prasit Palittapongarnpim,33 Henry B. Perdigon,6 Maude Elvira Phipps,1,34 Eileen Png,8 Yoshiyuki Sakaki,35 Jazelyn M. Salvador,6 Yuliana Sandraling,29 Vinod Scaria,2 Mark Seielstad,8 † Mohd Ros Sidek,14 Amit Sinha,2 Metawee Srikummool,19 Herawati Sudoyo,29 Sumio Sugano,37 Helena Suryadi,29 Yoshiyuki Suzuki,11 Kristina A. Tabbada,6 Adrian Tan,8 Katsushi Tokunaga,25 Sissades Tongsima,4 Lilian P. Villamor,6 Eric Wang,20,21 Ying Wang,15 Haifeng Wang,15 Jer￾Yuarn Wu,7 Huasheng Xiao,13 Shuhua Xu,38† Jin Ok Yang,5 Yin Yao Shugart,39 Hyang-Sook Yoo,5 Wentao Yuan,15 Guoping Zhao,15 Bin Alwi Zilfalil,14 Indian Genome Variation Consortium2 1 Department of Molecular Medicine, Faculty of Medicine, and the Department of Anthropology, Faculty of Arts and Social Sciences, University of Malaya, Kuala Lumpur, 50603, Malaysia. 2 Institute of Genomics and Integrative Biology, Council for Scientific and Industrial Research, Mall Road, Delhi 110007, India. 3 Mahidol University, Salaya Campus, 25/25 M. 3, Puttamonthon 4 Road, Puttamonthon, Nakornpathom 73170, Thailand. 4 Biostatistics and Informatics Laboratory, Genome Institute, National Center for Genetic Engineering and Biotechnology, Thailand Science Park, Pathumtani 12120, Thailand. 5 Korean BioInformation Center (KOBIC), Korea Re￾search Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Deajeon 305-806, Korea. 6 DNA Anal￾ysis Laboratory, Natural Sciences Research Institute, University of the Philippines, Diliman, Quezon City 1101, Philippines. 7 Institute of Biomedical Sciences, Academia Sinica, 128 Sec 2 Academia Road Nangang, Taipei City 115, Taiwan. 8 Genome Institute of Singapore, 60 Biopolis Street 02-01, 138672, Singapore. 9 Institute of Medical Biology, Chinese Academy of Medical Science, Kunming, China. 10Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, 625 Pedro Gil Street, Ermita Manila 1000, Philippines. 11Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. 12Bio￾medicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koto￾ku, Tokyo 135-0064, Japan. 13National Engineering Center for Biochip at Shanghai, 151 Li Bing Road, Shanghai 201203, China. 14Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. 15MOST-Shanghai Laboratory of Disease and Health Genomics, Chinese National Human Genome Center Shanghai, 250 Bi Bo Road, Shanghai 201203, China. 16Department of Molecular Life Science Division of Molecular Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-A Kanagawa-Pref A259-1193, Japan. 17State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sci￾ences, Fudan University, 220 Handan Road, Shanghai 200433, China. 18Korea National Institute of Health, 194, Tongil-Lo, Eunpyung-Gu, Seoul, 122-701, Korea. 19Department of Biol￾ogy, Faculty of Science, Chiang Mai University, 239 Huay Kaew Road, Chiang Mai 50202, Thailand. 20Genomics Collaborations, Affymetrix, 3420 Central Expressway, Santa Clara, CA 95051, USA. 21Veracyte, 7000 Shoreline Court, Suite 250, South San Francisco, CA 94080, USA. 22The Centre for Genomic Appli￾cations (an IGIB-IMM Collaboration), 254 Ground Floor, Phase III Okhla Industrial Estate, New Delhi 110020, India. 23Soongsil University, Sangdo-5-dong 1-1, Dongjak-gu, Seoul 156-743, Korea. 24Eulji University College of Medicine, 143-5 Yong-du￾dong Jung-gu, Dae-jeon City 301-832, Korea. 25Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. 26Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, 5 Lower Kent Ridge Road, 119074, Singapore. 27Population Genetics Lab, Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, 117510, Singapore. 28Indian Statistical Institute (Kolkata) 203 Barrack￾pore Trunk Road, Kolkata 700108, India. 29Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia. 30Informatics Experimental Therapeutic Centre, 31 Biopolis Way, 03-01 Nanos, 138669, Singapore. 31Division of Information Sciences, School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singa￾pore. 32Department of Medical Genetics, University of the Ryukyus Faculty of Medicine, Nishihara, 207 Uehara, Okinawa 903-0215, Japan. 33National Science and Technology Devel￾opment Agency, 111 Thailand Science Park, Pathumtani 12120, Thailand. 34Monash University (Sunway Campus), Jalan Lagoon Selatan, 46150 Bandar Sunway, Selangor, Malaysia. 35RIKEN Genomic Sciences Center, W502, 1-7-22 Suehiro-cho, Tsurumi￾ku, Yokohama 230-0045, Japan. 36Department of Biochem￾istry, University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sasson Road, Pokfulam, Hong Kong. 37Laboratory of Functional Genomics, Department of Medical Genome Sciences Graduate School of Frontier Sciences, Univer￾sity of Tokyo (Shirokanedai Laboratory), 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. 38Chinese Academy of Sciences-Max Planck Society Partner Institute for Computa￾tional Biology, Shanghai Institutes of Biological Sciences, Chi￾nese Academy of Sciences, 320 Yueyang Rd., Shanghai 200031, China. 39Genomic Research Branch, National Institute of Men￾tal Health, National Institutes of Health, 6001 Executive Bou￾levard, Bethesda, MD 20892 USA. 40Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, Tobetsu 061-0293, Japan. Supporting Online Material www.sciencemag.org/cgi/content/full/326/5959/1541/DC1 Materials and Methods SOM Text Figs. S1 to S38 Tables S1 to S4 1 June 2009; accepted 13 October 2009 10.1126/science.1177074 www.sciencemag.org SCIENCE VOL 326 11 DECEMBER 2009 1545 REPORTS