Genetic Evidence for High-Altitude Adaptation in Tibet

Simonson, Tatum S.; Yang, Yingzhong; Huff, Chad D.; Yun, Haixia; Qin, Ga; Witherspoon, David J.; Bai, Zhenzhong; Lorenzo, Felipe R.; Xing, Jinchuan; Jorde, Lynn B.; Prchal, Josef T.; Ge, RiLi

doi:10.1126/science.1189406

Cited by 1,227High Altitude and HypoxiaForensic and Genetic ResearchGenetics and Physical Performance

Genetic Evidence for High-Altitude Adaptation in Tibet

Simonson, Tatum S., Yang, Yingzhong, Huff, Chad D., Yun, Haixia, Qin, Ga, Witherspoon, David J., Bai, Zhenzhong, Lorenzo, Felipe R. +4 more·2010·Science

DOI 10.1126/science.1189406

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Abstract

No Genetic Vertigo: Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation in Tibetans, Simonson et al. (p. 72 , published online 13 May) conducted a genome scan of nucleotide polymorphism comparing Tibetans, Han Chinese, and Japanese, while Yi et al. (p. 75 ) performed comparable analyses on the coding regions of all genes—their exomes. Both studies converged on a gene, endothelial Per-Arnt-Sim domain protein 1 (also known as hypoxia-inducible factor 2 α), which has been linked to the regulation of red blood cell production. Other genes identified that were potentially under selection included adult and fetal hemoglobin and two functional candidate loci that were correlated with low hemoglobin concentration in Tibetans. Future detailed functional studies will now be required to examine the mechanistic underpinnings of physiological adaptation to high altitudes.

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Alleles of human ADAM17 were previously shown to be present at significantly different frequencies in Tibetans and low-altitude dwellers, indicating a possible role for this gene in altitude adaptation.
“Notably, alleles of human ADAM17 were previously shown to be present at significant different frequencies in Tibetans and low-altitude dwellers 36 , indicating a possible role for this gene in altitude adaptation.”
From The yak genome and adaptation to life at high altitude (2012) · cites this paper as [36]
Genetic variations in HIF2A, PHD2 and PPARA associate with lower hemoglobins in native Tibetans compared to Han Chinese and with high altitude adaptation in other populations.
“Genome-wide searches for single-nucleotide polymorphisms (SNP), candidate gene approaches and exome sequencing have identified genetic variations in the HIF2A, PHD2 and PPARA genes that associate with lower hemoglobins in native Tibetans compared to Han Chinese and with high altitude adaptation in other populations.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [176]

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Authors: Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., Bai, Z., Lorenzo, F. R., Xing, J., Jorde, L. B., Prchal, J. T., & Ge, R.
Affiliations: University of Utah (US)
Qinghai University (CN)
Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai 810001, People’s Republic of China.
Corresponding author: Yang, Yingzhong
Yun, Haixia
Bai, Zhenzhong
Jorde, Lynn B.
Prchal, Josef T.
ORCID: Simonson, Tatum S.
Huff, Chad D.
Bai, Zhenzhong
Xing, Jinchuan
Jorde, Lynn B.
Prchal, Josef T.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2010-07-02
Volume: 329
Issue: 5987
Pages: 72-75
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1189406
OpenAlex: W2047366062
Cited by: 1,227
References: 67
Citations by year: 2026: 79 · 2025: 72 · 2024: 66 · 2023: 101 · 2022: 70 · 2021: 84 · 2020: 92 · 2019: 78 · 2018: 75 · 2017: 67 · 2016: 64 · 2015: 95 · 2014: 82 · 2013: 67 · 2012: 66
FWCI: 35.97
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-50077, R01HL050077)
National Human Genome Research Institute (R00HG005846)
National Cancer Institute (P01CA108671)
National Institute of General Medical Sciences (R01GM059290, GM059290)
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK069513, DK 069513)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords: high-altitude adaptation, Tibetans, HIF-2α, EPAS1, genome-wide association study, nucleotide polymorphism, exome sequencing, natural selection, fetal hemoglobin, hemoglobin A, erythropoiesis, Tibetan Plateau
MeSH terms: Acclimatization, Altitude, Ethnicity, Female, Haplotypes, Hemoglobins, Humans, Male, Oxygen, Phenotype, Procollagen-Proline Dioxygenase, Selection, Genetic, Genetic Variation, Signal Transduction, Genome, Human, Linear Models, Tibet, Polymorphism, Single Nucleotide, Asian People, PPAR alpha, Hypoxia-Inducible Factor 1, Genetic Association Studies, Hypoxia-Inducible Factor-Proline Dioxygenases

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Genetic Evidence for High-Altitude Adaptation in Tibet

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