Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations
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Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and < 2.5% in the plains area. From the individual perspective, 87.57% of the individuals from the Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.
KeywordsTibetans Highland adaption Archaic haplotype SNP East Asian
We would like to thank all of the collaborators who helped to collect the samples. Special thanks are due to the hundreds of individuals who volunteered to give blood samples for studies of genetic diversity.
LJ planned the study, oversaw study data collection and analysis, and wrote the manuscript. JP and XY collected the blood samples. MH, LW, QM, and HZ designed and performed the experiments. JL assisted in statistical analysis. AJ supervised the project. CL supervised the project, provided financial support, and prepared the manuscript.
All authors approved the final manuscript.
This work was funded in part by the National Key Research and Development Program of China (2017YFC0803501) and the basic research project (2016JB039 and 2017JB027). Biological samples from the Caixia laboratory were funded by the National Infrastructure of Chinese Genetic Resources (NICGR: YCZYPT 01–3) and the basic research project (2017JB025).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 1.Zhao M, Kong QP, Wang HW, Peng MS, Xie XD, Wang WZ, Jiayang, Duan JG, Cai MC, Zhao SN, Cidanpingcuo, Tu YQ, Wu SF, Yao YG, Bandelt HJ, Zhang YP (2009) Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau. Proc Natl Acad Sci U S A 106(50):21230–21235. https://doi.org/10.1073/pnas.0907844106 CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Bigham A, Bauchet M, Pinto D, Mao X, Akey JM, Mei R, Scherer SW, Julian CG, Wilson MJ, Lopez Herraez D, Brutsaert T, Parra EJ, Moore LG, Shriver MD (2010) Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Genet 6(9):e1001116. https://doi.org/10.1371/journal.pgen.1001116 CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Beall CM, Cavalleri GL, Deng L, Elston RC, Gao Y, Knight J, Li C, Li JC, Liang Y, McCormack M, Montgomery HE, Pan H, Robbins PA, Shianna KV, Tam SC, Tsering N, Veeramah KR, Wang W, Wangdui P, Weale ME, Xu Y, Xu Z, Yang L, Zaman MJ, Zeng C, Zhang L, Zhang X, Zhaxi P, Zheng YT (2010) Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A 107(25):11459–11464. https://doi.org/10.1073/pnas.1002443107 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Qin Z, Yang Y, Kang L, Yan S, Cho K, Cai X, Lu Y, Zheng H, Zhu D, Fei D, Li S, Jin L, Li H (2010) A mitochondrial revelation of early human migrations to the Tibetan Plateau before and after the last glacial maximum. Am J Phys Anthropol 143(4):555–569. https://doi.org/10.1002/ajpa.21350 CrossRefPubMedGoogle Scholar
- 6.Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZX, Pool JE, Xu X, Jiang H, Vinckenbosch N, Korneliussen TS, Zheng H, Liu T, He W, Li K, Luo R, Nie X, Wu H, Zhao M, Cao H, Zou J, Shan Y, Li S, Yang Q, Asan, Ni P, Tian G, Xu J, Liu X, Jiang T, Wu R, Zhou G, Tang M, Qin J, Wang T, Feng S, Li G, Huasang, Luosang J, Wang W, Chen F, Wang Y, Zheng X, Li Z, Bianba Z, Yang G, Wang X, Tang S, Gao G, Chen Y, Luo Z, Gusang L, Cao Z, Zhang Q, Ouyang W, Ren X, Liang H, Huang Y, Li J, Bolund L, Kristiansen K, Li Y, Zhang Y, Zhang X, Li R, Yang H, Nielsen R, Wang J (2010) Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329(5987):75–78. https://doi.org/10.1126/science.1190371 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Peng Y, Yang Z, Zhang H, Cui C, Qi X, Luo X, Tao X, Wu T, Ouzhuluobu, Basang, Ciwangsangbu, Danzengduojie, Chen H, Shi H, Su B (2011) Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. Mol Biol Evol 28(2):1075–1081. https://doi.org/10.1093/molbev/msq290 CrossRefPubMedGoogle Scholar
- 8.Wang B, Zhang YB, Zhang F, Lin H, Wang X, Wan N, Ye Z, Weng H, Zhang L, Li X, Yan J, Wang P, Wu T, Cheng L, Wang J, Wang DM, Ma X, Yu J (2011) On the origin of Tibetans and their genetic basis in adapting high-altitude environments. PLoS One 6(2):e17002. https://doi.org/10.1371/journal.pone.0017002 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Xiang K, Ouzhuluobu PY, Yang Z, Zhang X, Cui C, Zhang H, Li M, Zhang Y, Bianba, Gonggalanzi, Basang, Ciwangsangbu, Wu T, Chen H, Shi H, Qi X, Su B (2013) Identification of a Tibetan-specific mutation in the hypoxic gene EGLN1 and its contribution to high-altitude adaptation. Mol Biol Evol 30(8):1889–1898. https://doi.org/10.1093/molbev/mst090 CrossRefPubMedGoogle Scholar
- 12.Huerta-Sanchez E, Jin X, Asan, Bianba Z, Peter BM, Vinckenbosch N, Liang Y, Yi X, He M, Somel M, Ni P, Wang B, Ou X, Huasang, Luosang J, Cuo ZX, Li K, Gao G, Yin Y, Wang W, Zhang X, Xu X, Yang H, Li Y, Wang J, Nielsen R (2014) Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 512(7513):194–197. https://doi.org/10.1038/nature13408 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Hackinger S, Kraaijenbrink T, Xue Y, Mezzavilla M, Asan, van Driem G, Jobling MA, de Knijff P, Tyler-Smith C, Ayub Q (2016) Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas. Hum Genet 135(4):393–402. https://doi.org/10.1007/s00439-016-1641-2 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Raymond M, Rousset F (1995) GENEPOP (version 1.2): population genetics software for exact tests and ecumenicism. J Hered 86(3):248–249. https://doi.org/10.1093/oxfordjournals.jhered.a111573 CrossRefGoogle Scholar
- 17.Team RDC (2011) R: a language and environment for statistical. Computing 14:12–21Google Scholar
- 18.Kolde R (2015) Pheatmap: pretty heatmaps. https://cran.rproject.org/web/packages/pheatmap/index.html. Accessed 11 Dec 2015