hybrid sterility involves both the unusual abun- References and notes 21. 1. E. Tomkiel, Genetica 109, 95(2000) dance and retention of OdsHmau protein in 1. E. Mayr, Systematics and the Ongin of the d. simulans testis. as well as an unusual ewpoint of a Zoologist ( Columbia Univ. 23. 0. Mihola. Z. Trachtulec ek, I C Schimenti J. Foret, Science 323, 373(2009) localization and possibly decondensation of the 2).A Coyne, H A Orr,Speciation (Sinauer N. Phadnis, H. A Orr, Science 323, 376(2009) D. simulans Y chromosome. We conclude on Sunderland, MA 2004). 25. K Sawamura. M. T Yamamoto, T. K Watanabe, Genetics the basis of these data that hybrid male sterility 3. C.C. Laurie, Genetics 147, 937(1997) 133.307(1993) is caused by a gain-of-function interaction be- 4. R. M. Kliman et al. Genetics 156, 1913(2000) tween OdsHmau and some component of the 5. C. T Ting, S. C. Tsaur, M. L. Wu, C. 1. Wu, Science 282, 27. N. ). Brideau et al, Science 314, 1292(2006). H. S. Malik, S. Henikoff, Cell 138, D. simulans Y chromosome heterochromatin, 6.S. Sun, C T. Ting, C. I. Wu, Science 305, 81(2004) 29. We thank C-l. Wu for the d. simulans fertile and sterile with this protein-DNA interaction representing 7. D. E Perez, C L Wu, Genetics 140, 201(1995). introgression lines; C. Ting for scientific discussions the Dobzhansky-Muller incompatibility and sharing data: G. Findlay for initial observations on Odsh shares similarities with the hybrid 134,261(1993) odsH cytology, and K. Ahmad, S. Biggins, N. Elde, S. Henikoff, N. Phadnis, T. Tsukiyama, and D. Vermaal sterility genes Prdm9 (or Meisetz) in mouse(23) 10. C.T. Ting et al, Proc. NatL. Acad. Sci. U.SA.101, 12232 comments ed by nih and Overdrive(Ovd) in Drosophila(24), all of (2004) training grant PHS NRSA 132 GM07270(]].B which encode proteins with putative DNA- 11. K Tabuchi, 5. Yoshikawa, Y Yuasa, K Sawamoto and grants from the Mathers binding domains. Satellite DNAs have also 12. M. Nei, 1. Zhang, Science 282, 1428(1998) NIH RO1-GM74108(HS M ) H.S.M. is an Early-Career Scientist of the Howard Hughes Medical Institute. been implicated in hybrid inviability, including 13. S Henikoff. K Ahmad, H.S. Malik, Science 293, 1098(2001) a pericentric satellite locus(Zhr)(25, 26) and a 14. S. Henikoff, H S Malik, Nature 417, 227(2002) ting Online Material gene encoding a heterochromatin-binding pro- 15. L Fishman, A Saunders,, Science 322, 1559(2008) tein(hr)(27). Thus, rapidly evolving repetitive 16. A Daner er al. Mold. ele e: oL 22. 52 DNA elements driven by genetic conflict may 18. M Ashburner, KG.Golic, RSHawley, Drosophila represent a major evolutionary force driving A Laboratory Handbook(Cold Spring Harbor Laboratory sequence divergence of speciation genes that would 10 September 2009: accepted 13 october 2009 ultimately result in hybrid incompatibilities 19. G. cendi 20. B. D. McKee, Curr. Top. Dev. Biol. 37, 77(1998) Include this information when citing this paper Mapping Human Genetic Diversity in Asia by geographe primit, b a knw n histoy or The HUGO Pan-Asian SNP Consortium*t admixture, or, especially at higher Ks, by mem- bership in a small population isolate. The results ia harbors substantial cultural and linguistic diversity, but the geographic structure of obtained using frappe(In), a maximum-likehhoodH based clustering analysis, showed a general con- genetic variation across the continent remains enigmatic. Here we report a large-scale survey of cordance with those of struCture utosomal variation from a broad geographic sample of Asian human populations. Our results Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene lor y.u26). These analyses show that most individ- show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography within a population share very similar an- cestry estimates at all Ks, an observation that is Southeast Asian(SEA) or Central-South Asian(CSA) populations and show clinal structure with viduals(fig. $27)based on an allele-sharing dis- haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were tance(12). Therefore, we proceeded to evaluate found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic the relationships among populations. A maximum source of EA populations likelihood tree of populations, based on 42, 793 SNPs whose ancestral states were known(Fig. S ontinental relationships, or fine-scale struc We first performed a Bayesian clustering pro- by 100% of bootstrap replicates. This pattern re- ture in Europe, have been published recently (1-8). cedure using the STRUCtUre algorithm (10) mained even after data from 51 additional popu- Asian(SEA) and East Asian(EA)populations by person is posited to derive from an arbitrary num- recent study were integrated into the tree fe We have extended this approach to Southeast to examine the ancestry of each individual. Each lations and 19, 934 commonly typed SNPs from sing the Affymetrix Gene Chip Human Mapping ber of ancestral populations, denoted by K. We ran S28). These observations suggest that SEA and 50K Xba Array. Stringently quality-controlled STRUCTURE from K=2 to K= 14 using both EA populations share a common origin. genotypes were obtained at 54, 794 autosomal the complete data set and SNP subsets to exclude STRUCTURElfrappe and principal compo- single-nucleotide polymorphisms(SNPs)in 1928 those in strong linkage disequilibrium(Fig. I and nents analyses(PCA)(13)(Figs. I and 2 and figs. individuals representing 73 Asian and two non- figs. SI to S13). AtK=2 andk =3, all SEA and SI to $26) identify as many as 10 main popula- Asian Hap Map populations(9). Apart from de- EA samples are united by predominant member- tion components. Each component corresponds veloping a general description of Asian population ship in a common cluster, with the other cluster(s) largely to one of the five major linguistic groups structure and its relation to geography, language, corresponding largely to Indo-European(E)and (Altaic, Sino-Tibetan/Tai-Kadai, Hmong-Mien, and demographic history, we concentrated on un- African(AF)ancestries. At K= 4, a component Austro-Asiatic, and Austronesian), three ethnic most frequently found in Negrito populations that categones(Philippine Negritos, Malaysian Negritos, All authors with their affiliations appear at the end of this is also shared by all SEA populations emerges, and East Indonesians/Melanesians)and two small uggesting a common SEA ancestry. Each value population isolates(the Bidayuh of Borneo and in007@gmail com(LJ): liue @gis. d-star. edu.sg (ET. ); of K beyond 4 introduces a new component that the hunter-gatherer Mlabri population of central elstadm@gisa-star. edu.sg (M.S. ); xushua@picb ac cn(Sx) tends to be associated with a group of popula- and northem Thailand). The STRUCTURe results www.sciencemag.orgScieNceVol32611DecembEr2009 1541hybrid sterility involves both the unusual abun￾dance and retention of OdsHmau protein in the D. simulans testis, as well as an unusual localization and possibly decondensation of the D. simulans Y chromosome. We conclude on the basis of these data that hybrid male sterility is caused by a gain-of-function interaction be￾tween OdsHmau and some component of the D. simulans Y chromosome heterochromatin, with this protein-DNA interaction representing the Dobzhansky-Muller incompatibility. OdsH shares similarities with the hybrid sterility genes Prdm9 (or Meisetz) in mouse (23) and Overdrive (Ovd) in Drosophila (24), all of which encode proteins with putative DNA￾binding domains. Satellite DNAs have also been implicated in hybrid inviability, including a pericentric satellite locus (Zhr) (25, 26) and a gene encoding a heterochromatin-binding pro￾tein (Lhr) (27). Thus, rapidly evolving repetitive DNA elements driven by genetic conflict may represent a major evolutionary force driving sequence divergence of speciation genes that would ultimately result in hybrid incompatibilities (13, 14, 28). References and Notes 1. E. Mayr, Systematics and the Origin of Species from the Viewpoint of a Zoologist (Columbia Univ. Press, New York, 1942). 2. J. A. Coyne, H. A. Orr, Speciation (Sinauer Associates, Sunderland, MA, 2004). 3. C. C. Laurie, Genetics 147, 937 (1997). 4. R. M. Kliman et al., Genetics 156, 1913 (2000). 5. C. T. Ting, S. C. Tsaur, M. L. Wu, C. I. Wu, Science 282, 1501 (1998). 6. S. Sun, C. T. Ting, C. I. Wu, Science 305, 81 (2004). 7. D. E. Perez, C. I. Wu, Genetics 140, 201 (1995). 8. D. E. Perez, C. I. Wu, N. A. Johnson, M. L. Wu, Genetics 134, 261 (1993). 9. S. D. Hueber, I. Lohmann, Bioessays 30, 965 (2008). 10. C. T. Ting et al., Proc. Natl. Acad. Sci. U.S.A. 101, 12232 (2004). 11. K. Tabuchi, S. Yoshikawa, Y. Yuasa, K. Sawamoto, H. Okano, Neurosci. Lett. 257, 49 (1998). 12. M. Nei, J. Zhang, Science 282, 1428 (1998). 13. S. Henikoff, K. Ahmad, H. S. Malik, Science 293, 1098 (2001). 14. S. Henikoff, H. S. Malik, Nature 417, 227 (2002). 15. L. Fishman, A. Saunders, Science 322, 1559 (2008). 16. A. Daniel, Am. J. Med. Genet. 111, 450 (2002). 17. N. Aulner et al., Mol. Cell. Biol. 22, 1218 (2002). 18. M. Ashburner, K. G. Golic, R. S. Hawley, Drosophila: A Laboratory Handbook (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, ed. 2, 2005). 19. G. Cenci, S. Bonaccorsi, C. Pisano, F. Verni, M. Gatti, J. Cell Sci. 107, 3521 (1994). 20. B. D. McKee, Curr. Top. Dev. Biol. 37, 77 (1998). 21. J. E. Tomkiel, Genetica 109, 95 (2000). 22. J. Forejt, Trends Genet. 12, 412 (1996). 23. O. Mihola, Z. Trachtulec, C. Vlcek, J. C. Schimenti, J. Forejt, Science 323, 373 (2009). 24. N. Phadnis, H. A. Orr, Science 323, 376 (2009). 25. K. Sawamura, M. T. Yamamoto, T. K. Watanabe, Genetics 133, 307 (1993). 26. P. M. Ferree, D. A. Barbash, PLoS Biol. 7, e1000234 (2009). 27. N. J. Brideau et al., Science 314, 1292 (2006). 28. H. S. Malik, S. Henikoff, Cell 138, 1067 (2009). 29. We thank C-I. Wu for the D. simulans fertile and sterile introgression lines; C. Ting for scientific discussions and sharing data; G. Findlay for initial observations on OdsH cytology; and K. Ahmad, S. Biggins, N. Elde, S. Henikoff, N. Phadnis, T. Tsukiyama, and D. Vermaak for comments on the manuscript. Supported by NIH training grant PHS NRSA T32 GM07270 (J.J.B.), and grants from the Mathers foundation and NIH R01-GM74108 (H.S.M.). H.S.M. is an Early-Career Scientist of the Howard Hughes Medical Institute. Supporting Online Material www.sciencemag.org/cgi/content/full/1181756/DC1 Materials and Methods Figs. S1 to S8 References 10 September 2009; accepted 13 October 2009 Published online 22 October 2009; 10.1126/science.1181756 Include this information when citing this paper. Mapping Human Genetic Diversity in Asia The HUGO Pan-Asian SNP Consortium*† Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations. Several genome-wide studies of human ge￾netic diversity focusing primarily on broad continental relationships, or fine-scale struc￾ture in Europe, have been published recently (1–8). We have extended this approach to Southeast Asian (SEA) and East Asian (EA) populations by using the Affymetrix GeneChip Human Mapping 50K Xba Array. Stringently quality-controlled genotypes were obtained at 54,794 autosomal single-nucleotide polymorphisms (SNPs) in 1928 individuals representing 73 Asian and two non￾Asian HapMap populations (9). Apart from de￾veloping a general description of Asian population structure and its relation to geography, language, and demographic history, we concentrated on un￾covering the geographic source(s) of EA and SEA populations. We first performed a Bayesian clustering pro￾cedure using the STRUCTURE algorithm (10) to examine the ancestry of each individual. Each person is posited to derive from an arbitrary num￾ber of ancestral populations, denoted by K. We ran STRUCTURE from K = 2 to K = 14 using both the complete data set and SNP subsets to exclude those in strong linkage disequilibrium (Fig. 1 and figs. S1 to S13). At K = 2 and K = 3, all SEA and EA samples are united by predominant member￾ship in a common cluster, with the other cluster(s) corresponding largely to Indo-European (IE) and African (AF) ancestries. At K = 4, a component most frequently found in Negrito populations that is also shared by all SEA populations emerges, suggesting a common SEA ancestry. Each value of K beyond 4 introduces a new component that tends to be associated with a group of popula￾tions united by membership in a linguistic family, by geographic proximity, by a known history of admixture, or, especially at higher Ks, by mem￾bership in a small population isolate. The results obtained using frappe (11), a maximum-likelihood– based clustering analysis, showed a general con￾cordance with those of STRUCTURE (figs. S14 to S26). These analyses show that most individ￾uals within a population share very similar an￾cestry estimates at all Ks, an observation that is consistent also with a phylogeny relating indi￾viduals (fig. S27) based on an allele-sharing dis￾tance (12). Therefore, we proceeded to evaluate the relationships among populations. A maximum￾likelihood tree of populations, based on 42,793 SNPs whose ancestral states were known (Fig. 1), showed that all the SEA and EA populations make up a monophyletic clade that is supported by 100% of bootstrap replicates. This pattern re￾mained even after data from 51 additional popu￾lations and 19,934 commonly typed SNPs from a recent study were integrated into the tree (fig. S28). These observations suggest that SEA and EA populations share a common origin. STRUCTURE/frappe and principal compo￾nents analyses (PCA) (13) (Figs. 1 and 2 and figs. S1 to S26) identify as many as 10 main popula￾tion components. Each component corresponds largely to one of the five major linguistic groups (Altaic, Sino-Tibetan/Tai-Kadai, Hmong-Mien, Austro-Asiatic, and Austronesian), three ethnic categories (Philippine Negritos, Malaysian Negritos, and East Indonesians/Melanesians) and two small population isolates (the Bidayuh of Borneo and the hunter-gatherer Mlabri population of central and northern Thailand). The STRUCTURE results *All authors with their affiliations appear at the end of this paper. †To whom correspondence should be addressed. E-mail: ljin007@gmail.com (L.J.); liue@gis.a-star.edu.sg (E.T.L.); seielstadm@gis.a-star.edu.sg (M.S.); xushua@picb.ac.cn (S.X.) www.sciencemag.org SCIENCE VOL 326 11 DECEMBER 2009 1541 REPORTS