Genetic Variations in Tibetan Populations and High-Altitude Adaptation at the Himalayas
Open accessAbstract
Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.
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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 [177]
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- Authors
- 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.
- Affiliations
- Kunming Institute of Zoology (CN)
- Tibet University (CN)
- Harvard University (US)
- Corresponding author
- Shi, H.
- Su, B.
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-28
- Volume
- 28
- Issue
- 2
- Pages
- 1075-1081
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2109099152
- Cited by
- 388
- References
- 4
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 24 · 2023: 25 · 2022: 21 · 2021: 26 · 2020: 26 · 2019: 28 · 2018: 21 · 2017: 29 · 2016: 28 · 2015: 40 · 2014: 38 · 2013: 32 · 2012: 16
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30771181, 973 Project, 30700445, 30630013)
- Chinese Academy of Sciences
- Natural Science Foundation of Yunnan Province (2007C100M, 2009CD107)
- State Key Laboratory of Genetic Resources and Evolution
- 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 › Evolution and Genetic Dynamics
- Keywords
- Tibetan population, high-altitude adaptation, hypoxia, EPAS1, EGLN1, selective sweeps, natural selection, genetic variation, haplotypes, Himalaya
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Altitude Sickness, China, Gene Frequency, Genetics, Population, Humans, Procollagen-Proline Dioxygenase, Tibet, Polymorphism, Single Nucleotide, Asian People, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Genome-Wide Association Study, Hypoxia-Inducible Factor-Proline Dioxygenases
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