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Cited by 28Forensic and Genetic ResearchGenetic diversity and population structureGenetic Associations and Epidemiology

The fine-scale genetic structure and evolution of the Japanese population

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Takeuchi, Fumihiko, Katsuya, Tomohiro, Kimura, Ryosuke, Nabika, Toru, Isomura, Minoru, Ohkubo, Takayoshi, Tabara, Yasuharu, Yamamoto, Ken +9 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0185487PMC PMC5665431
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Abstract

The contemporary Japanese populations largely consist of three genetically distinct groups-Hondo, Ryukyu and Ainu. By principal-component analysis, while the three groups can be clearly separated, the Hondo people, comprising 99% of the Japanese, form one almost indistinguishable cluster. To understand fine-scale genetic structure, we applied powerful haplotype-based statistical methods to genome-wide single nucleotide polymorphism data from 1600 Japanese individuals, sampled from eight distinct regions in Japan. We then combined the Japanese data with 26 other Asian populations data to analyze the shared ancestry and genetic differentiation. We found that the Japanese could be separated into nine genetic clusters in our dataset, showing a marked concordance with geography; and that major components of ancestry profile of Japanese were from the Korean and Han Chinese clusters. We also detected and dated admixture in the Japanese. While genetic differentiation between Ryukyu and Hondo was suggested to be caused in part by positive selection, genetic differentiation among the Hondo clusters appeared to result principally from genetic drift. Notably, in Asians, we found the possibility that positive selection accentuated genetic differentiation among distant populations but attenuated genetic differentiation among close populations. These findings are significant for studies of human evolution and medical genetics.

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  • Even within the same country, there are several subpopulations with slightly different genetic backgrounds.

    “Even within the same country, there are several subpopulations with slightly different genetic backgrounds [33, 34].”

    From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [34]

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  1. [1]Jinam TA, Kanzawa-Kiriyama H, Saitou N. Human genetic diversity in the Japanese Archipelago: dual structure and beyond. Genes Genet Syst. 2015; 90: 147– 152. doi: 10.1266/ggs.90.147 26510569 · DOI
  2. [2]Yamaguchi-Kabata Y, Nakazono K, Takahashi A, Saito S, Hosono N, Kubo M, et al Japanese Population Structure, Based on SNP Genotypes from 7003 Individuals Compared to Other Ethnic Groups: Effects on Population-Based Association Studies. The American Journal of Human Genetics. 2008; 83: 445– 456. doi: 10.1016/j.ajhg.2008.08.019 18817904 PMC2561928 · DOI
  3. [3]Japanese Archipelago Human Population Genetics Consortium, Jinam T, Nishida N, Hirai M, Kawamura S, Oota H, et al The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan populations. J Hum Genet. 2012; 57: 787– 795. doi: 10.1038/jhg.2012.114 23135232 · DOI
  4. [4]Hanihara K. Dual Structure Model for the Population History of the Japanese. Japan Review. 1991; 2: 1– 33.
  5. [5]Imamura K. Prehistoric Japan: New Perspective on Insular East Asia. Hawaii: University of Hawaii Press; 1996.
  6. [7]Horai S, Murayama K, Hayasaka K, Matsubayashi S, Hattori Y, Fucharoen G, et al mtDNA polymorphism in East Asian Populations, with special reference to the peopling of Japan. Am J Hum Genet. 1996; 59: 579– 590. 8751859 PMC1914908
  7. [8]Tanaka M, Cabrera VM, González AM, Larruga JM, Takeyasu T, Fuku N, et al Mitochondrial genome variation in eastern Asia and the peopling of Japan. Genome Res. 2004; 14: 1832– 1850. doi: 10.1101/gr.2286304 15466285 PMC524407 · DOI
  8. [9]Hammer MF, Horai S. Y chromosomal DNA variation and the peopling of Japan. Am J Hum Genet. 1995; 56: 951– 962. 7717406 PMC1801189
  9. [10]Tajima A, Hayami M, Tokunaga K, Juji T, Matsuo M, Marzuki S, et al Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages. J Hum Genet. 2004; 49: 187– 193. doi: 10.1007/s10038-004-0131-x 14997363 · DOI
  10. [11]Hammer MF, Karafet TM, Park H, Omoto K, Harihara S, Stoneking M, et al Dual origins of the Japanese: common ground for hunter-gatherer and farmer Y chromosomes. J Hum Genet. 2006; 51: 47– 58. doi: 10.1007/s10038-005-0322-0 16328082 · DOI
  11. [12]Omoto K, Saitou N. Genetic origins of the Japanese: a partial support for the dual structure hypothesis. Am J Phys Anthropol. 1997; 102: 437– 446. doi: 10.1002/(SICI)1096-8644(199704)102:4<437::AID-AJPA1>3.0.CO;2-P 9140536 · DOI
  12. [13]Igawa K, Manabe Y, Oyamada J, Kitagawa Y, Kato K, Ikematsu K, et al Mitochondrial DNA analysis of Yayoi period human skeletal remains from the Doigahama site. J Hum Genet. 2009; 54: 581– 588. doi: 10.1038/jhg.2009.81 19696790 · DOI
  13. [14]Kanzawa-Kiriyama H, Saso A, Suwa G, Saitou N. Ancient mitochondrial DNA sequences of Jomon teeth samples from Sanganji, Tohoku district, Japan. Anthropological Science. 2013; 121: 89– 103. doi: 10.1537/ase.121113 · DOI
  14. [15]Jinam TA, Kanzawa-Kiriyama H, Inoue I, Tokunaga K, Omoto K, Saitou N. Unique characteristics of the Ainu population in Northern Japan. J Hum Genet. 2015; 60: 565– 571. doi: 10.1038/jhg.2015.79 26178428 · DOI
  15. [16]Kanzawa-Kiriyama H, Kryukov K, Jinam TA, Hosomichi K, Saso A, Suwa G, et al A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan. J Hum Genet. 2017; 62: 213– 221. doi: 10.1038/jhg.2016.110 27581845 PMC5285490 · DOI
  16. [17]Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000; 155: 945– 959. 10835412 PMC1461096
  17. [18]Patterson N, Price AL, Reich D. Population Structure and Eigenanalysis. PLoS Genet. 2006; 2: e190 doi: 10.1371/journal.pgen.0020190 17194218 PMC1713260 · DOI · Paper page
  18. [20]Leslie S, Winney B, Hellenthal G, Davison D, Boumertit A, Day T, et al The fine-scale genetic structure of the British population. Nature. 2015; 519: 309– 314. doi: 10.1038/nature14230 25788095 PMC4632200 · DOI
  19. [21]Price AL, Zaitlen NA, Reich D, Patterson N. New approaches to population stratification in genome-wide association studies. Nat Rev Genet. 2010; 11: 459– 463. doi: 10.1038/nrg2813 20548291 PMC2975875 · DOI
  20. [22]Kumasaka N, Yamaguchi-Kabata Y, Takahashi A, Kubo M, Nakamura Y, Kamatani N. Establishment of a standardized system to perform population structure analyses with limited sample size or with different sets of SNP genotypes. J Hum Genet. 2010; 55: 525– 533. doi: 10.1038/jhg.2010.63 20555335 · DOI
  21. [23]Devlin B, Roeder K, Wasserman L. Genomic control, a new approach to genetic-based association studies. Theoretical Population Biology. 2001; 60: 155– 166. doi: 10.1006/tpbi.2001.1542 11855950 · DOI
  22. [24]Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, Ramachandran S, et al Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation. Science. 2008; 319: 1100– 1104. doi: 10.1126/science.1153717 18292342 · DOI
  23. [25]HUGO Pan-Asian SNP Consortium, Abdulla MA, Ahmed I, Assawamakin A, Bhak J, Brahmachari SK, et al Mapping human genetic diversity in Asia. Science. 2009; 326: 1541– 1545. doi: 10.1126/science.1177074 20007900 · DOI
  24. [26]Loh P-R, Lipson M, Patterson N, Moorjani P, Pickrell JK, Reich D, et al Inferring admixture histories of human populations using linkage disequilibrium. Genetics. 2013; 193: 1233– 1254. doi: 10.1534/genetics.112.147330 23410830 PMC3606100 · DOI · Paper page
  25. [27]Alexander DH, Novembre J, Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. Cold Spring Harbor Lab; 2009; 19: 1655– 1664. doi: 10.1101/gr.094052.109 19648217 PMC2752134 · DOI · Paper page
  26. [28]Liu X, Ong RTH, Pillai EN, Elzein AM, Small KS, Clark TG, et al Detecting and characterizing genomic signatures of positive selection in global populations. Am J Hum Genet. 2013; 92: 866– 881. doi: 10.1016/j.ajhg.2013.04.021 23731540 PMC3675259 · DOI
  27. [29]Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, et al Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Cell. 2013; 152: 691– 702. doi: 10.1016/j.cell.2013.01.016 23415220 PMC3575602 · DOI
  28. [30]Li H, Borinskaya S, Yoshimura K, Kal'ina N, Marusin A, Stepanov VA, et al Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant. Ann Human Genet. 2009; 73: 335– 345. doi: 10.1111/j.1469-1809.2009.00517.x 19456322 PMC2846302 · DOI
  29. [31]Luo H-R, Wu G-S, Pakstis AJ, Tong L, Oota H, Kidd KK, et al Origin and dispersal of atypical aldehyde dehydrogenase ALDH2487Lys. Gene. 2009; 435: 96– 103. doi: 10.1016/j.gene.2008.12.021 19393179 · DOI
  30. [32]Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, et al Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet. 2011; 43: 531– 538. doi: 10.1038/ng.834 21572416 PMC3158568 · DOI
  31. [33]Ohashi J, Naka I, Tsuchiya N. The Impact of Natural Selection on an ABCC11 SNP Determining Earwax Type. Mol Biol Evol. 2010; 28: 849– 857. doi: 10.1093/molbev/msq264 20937735 · DOI
  32. [35]Fujimoto A, Kimura R, Ohashi J, Omi K, Yuliwulandari R, Batubara L, et al A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness. Hum Mol Genet. 2008; 17: 835– 843. doi: 10.1093/hmg/ddm355 18065779 · DOI · Paper page
  33. [36]Kimura R, Yamaguchi T, Takeda M, Kondo O, Toma T, Haneji K, et al A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am J Hum Genet. 2009; 85: 528– 535. doi: 10.1016/j.ajhg.2009.09.006 19804850 PMC2756549 · DOI
  34. [37]Oota H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SLB, et al The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination. Ann Human Genet. 2004; 68: 93– 109. 15008789
  35. [38]Yoshiura K-I, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, et al A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet. 2006; 38: 324– 330. doi: 10.1038/ng1733 16444273 · DOI
  36. [40]Han Y, Gu S, Oota H, Osier MV, Pakstis AJ, Speed WC, et al Evidence of positive selection on a class I ADH locus. Am J Hum Genet. 2007; 80: 441– 456. doi: 10.1086/512485 17273965 PMC1821113 · DOI
  37. [41]Osier MV, Pakstis AJ, Soodyall H, Comas D, Goldman D, Odunsi A, et al A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am J Hum Genet. 2002; 71: 84– 99. doi: 10.1086/341290 12050823 PMC384995 · DOI
  38. [42]Jeong C, Nakagome S, Di Rienzo A. Deep History of East Asian Populations Revealed Through Genetic Analysis of the Ainu. Genetics. Genetics; 2016; 202: 261– 272. doi: 10.1534/genetics.115.178673 26500257 PMC4701090 · DOI
  39. [43]Moorjani P, Patterson N, Hirschhorn JN, Keinan A, Hao L, Atzmon G, et al The history of African gene flow into Southern Europeans, Levantines, and Jews. PLoS Genet. 2011; 7: e1001373 doi: 10.1371/journal.pgen.1001373 21533020 PMC3080861 · DOI
  40. [45]Holsinger KE, Weir BS. Genetics in geographically structured populations: defining, estimating and interpreting F(ST). Nat Rev Genet. 2009; 10: 639– 650. doi: 10.1038/nrg2611 19687804 PMC4687486 · DOI
  41. [46]Livingstone FB. Gene frequency clines of the beta-hemoglobin locus in various human populations and their simulation by models involving differential selection. Hum Biol. 1969; 41: 223– 236. 5808784
  42. [47]Amato R, Pinelli M, Monticelli A, Marino D, Miele G, Cocozza S. Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases. PLoS ONE. 2009; 4: e7927 doi: 10.1371/journal.pone.0007927 19936260 PMC2775949 · DOI
  43. [48]Athanasiadis G, Cheng JY, Vilhjálmsson BJ, Jørgensen FG, Als TD, Le Hellard S, et al Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity. Genetics. Genetics; 2016; 204: 711– 722. doi: 10.1534/genetics.116.189241 27535931 PMC5068857 · DOI
  44. [49]Gattepaille LM, Jakobsson M. Combining markers into haplotypes can improve population structure inference. Genetics. 2012; 190: 159– 174. doi: 10.1534/genetics.111.131136 21868606 PMC3249356 · DOI
  45. [50]Lawson DJ, Falush D. Population identification using genetic data. Annu Rev Genom Human Genet. 2012; 13: 337– 361. doi: 10.1146/annurev-genom-082410-101510 22703172 · DOI · Paper page
  46. [51]Liu X, Lu D, Saw W-Y, Shaw PJ, Wangkumhang P, Ngamphiw C, et al Characterising private and shared signatures of positive selection in 37 Asian populations. Eur J Hum Genet. 2017; 25: 499– 508. doi: 10.1038/ejhg.2016.181 28098149 PMC5386408 · DOI
  47. [52]The International HapMap 3 Consortium. Integrating common and rare genetic variation in diverse human populations. Nature. 2010; 467: 52– 58. doi: 10.1038/nature09298 20811451 PMC3173859 · DOI · Paper page
  48. [53]Teo Y-Y, Sim X, Ong RTH, Tan AKS, Chen J, Tantoso E, et al Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations. Genome Res. 2009; 19: 2154– 2162. doi: 10.1101/gr.095000.109 19700652 PMC2775604 · DOI
  49. [54]Xing J, Watkins WS, Shlien A, Walker E, Huff CD, Witherspoon DJ, et al Toward a more uniform sampling of human genetic diversity: a survey of worldwide populations by high-density genotyping. Genomics. 2010; 96: 199– 210. doi: 10.1016/j.ygeno.2010.07.004 20643205 PMC2945611 · DOI
  50. [55]Purcell S, Neale B, Toddbrown K, Thomas L, Ferreira M, Bender D, et al PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics. 2007; 81: 559– 575. doi: 10.1086/519795 17701901 PMC1950838 · DOI · Paper page
  51. [56]McGinnis RE, Deloukas P, Mclaren WM, Inouye M. Visualizing chromosome mosaicism and detecting ethnic outliers by the method of “rare” heterozygotes and homozygotes (RHH). Hum Mol Genet. 2010; 19: 2539– 2553. doi: 10.1093/hmg/ddq102 20211853 PMC2883336 · DOI
  52. [57]Browning S, Browning B. Rapid and Accurate Haplotype Phasing and Missing-Data Inference for Whole-Genome Association Studies By Use of Localized Haplotype Clustering. The American Journal of Human Genetics. 2007; 81: 1084– 1097. doi: 10.1086/521987 17924348 PMC2265661 · DOI
  53. [58]Delaneau O, Zagury J-F, Marchini J. Improved whole-chromosome phasing for disease and population genetic studies. Nat Meth. Nature Publishing Group; 2013; 10: 5– 6. doi: 10.1038/nmeth.2307 23269371 · DOI
  54. [59]Paradis E. pegas: an R package for population genetics with an integrated-modular approach. Bioinformatics. 2010; 26: 419– 420. doi: 10.1093/bioinformatics/btp696 20080509 · DOI
  55. [60]Weir BS, Cockerham C. Estimating F-statistics for the analysis of population structure. Evolution. 1984; 38: 1358– 1370. doi: 10.1111/j.1558-5646.1984.tb05657.x 28563791 · DOI
  56. [61]Bhatia G, Patterson N, Sankararaman S, Price AL. Estimating and interpreting FST: the impact of rare variants. Genome Res. 2013; 23: 1514– 1521. doi: 10.1101/gr.154831.113 23861382 PMC3759727 · DOI · Paper page
  57. [62]Paradis E, Claude J, Strimmer K. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics. 2004; 20: 289– 290. doi: 10.1093/bioinformatics/btg412 14734327 · DOI
  58. [64]Hall P, Wilson SR. Two Guidelines for Bootstrap Hypothesis Testing. Biometrics. 1991; 47: 757 doi: 10.2307/2532163 · DOI · Paper page

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Authors
Takeuchi, F., Katsuya, T., Kimura, R., Nabika, T., Isomura, M., Ohkubo, T., Tabara, Y., Yamamoto, K., Yokota, M., Liu, X., Saw, W.-Y., Mamatyusupu, D., Yang, W., Xu, S., Japanese Genome Variation Consortium, Teo, Y.-Y., & Kato, N.
Affiliations
  • National Center for Global Health and Medicine (JP)
  • The University of Osaka (JP)
  • University of the Ryukyus (JP)
  • Shimane University (JP)
  • Teikyo University (JP)
  • Kyoto University (JP)
  • Kurume University (JP)
  • Aichi Gakuin University (JP)
  • National University of Singapore (SG)
  • Xinjiang University (CN)
  • Ningxia Medical University (CN)
  • Max Planck Society (DE)
  • Agency for Science, Technology and Research (SG)
Corresponding author
  • Takeuchi, Fumihiko
  • Kato, Norihiro
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-11-01
Volume
12
Issue
11
Pages
e0185487
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0185487
PMC
PMC5665431
OpenAlex
W2766436659
Cited by
28
References
4
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 1 · 2017: 1
FWCI
2.48
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (publishedVersion, cc-by)
  • National University of Singapore (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • University of the Ryukyus academic repository (University of the Ryukyus) (submittedVersion, cc-by)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • University oh the Ryukyus Repository (submittedVersion, cc-by-nc-nd)
Funders
  • National Center for Global Health and Medicine
  • National Research Foundation
  • National University of Singapore
  • National Research Foundation Singapore (NRF-RF-2010-05)
  • Ministry of Education, Culture, Sports, Science and Technology
  • National Natural Science Foundation of China (31525014, 91331204)
  • SENSHIN Medical Research Foundation
  • Program of Shanghai Subject Chief Scientist
  • Japan Society for the Promotion of Science (15K05577, 26290067, 17H04123)
  • National Science Fund for Distinguished Young Scholars (31525014)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
fine-scale genetic structure, Hondo, Ryukyu Islands, Ainu, admixture, positive selection, genetic drift, genetic differentiation, shared ancestry, East Asian populations, Han Chinese
MeSH terms
Multigene Family, Humans, Japan, Polymorphism, Single Nucleotide, Asian People, Genome-Wide Association Study

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