Shixuan Zhang
La Yang
Deji Quzong
Yi Li
Yanyun Ma
Meng Hao
WeiLin Pu
Xiaoyu Liu
Hongjun Xie
Meng Liang
Jiucun Wang
Qiangba Danzeng
a. High Altitude Medical Research Center of Tibet University/Center of Tibetan Studies (Everest Research Institute), Tibet University, 10 East Zangda Road, Lhasa, Tibet 850000, China;
b. State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China;
c. Institute for Six-sector Economy, Fudan University, Shanghai 200433, China;
d. Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China;
e. Tibet University-Fudan University Joint Laboratory for Biodiversity and Global Change, Tibet University, 10 East Zangda Road, Lhasa, Tibet 850000, China
Funds: [2019] No. 1-19
We are most grateful to all the individuals who participated in this study, especially the Chinese Tibet Mountaineering Team, for their contributions to this study. This work was supported by grants from: The Science and Technology Department of Tibet (08080002), 2019 School-level Cultivation Project of Tibet University (ZDTSJH19-08), and the Special Funds from the Central Finance to Support the Development of Local Universities (ZFYJY201902011. Index of Tibetan Finance and Education [2018] No. 54
[2020] No.79). This work was also supported by the Postdoctoral Science Foundation of China (2018M640333), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), Science and Technology Committee of Shanghai Municipality (18490750300), and Major Project of Special Development Funds of Zhangjiang National Independent Innovation Demonstration Zone (ZJ2019-ZD-004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Received Date: 2020-11-02
Accepted Date:2021-05-30
Rev Recd Date:2021-05-20
Publish Date:2021-07-06
Abstract
Abstract
High altitude is an extreme environment that imposes hypoxic pressure on physiological processes, and natives living at high altitudes are more adaptive in certain physiological processes. So far, epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood. Here, we recruit 32 Tibetan elite alpinists (TEAs), who have successfully mounted Everest (8848 m) at least five times. Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers (non-TEAs) are collected for analysis. Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs (Padj <0.05, |β| >0.1) between the two groups. Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L, MAP3K7CL, SEPTI-9, and CUL2. In addition, Gene ontology enrichment analysis reveals several inflammation-related pathways. Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups. In particular, TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count, platelet count, and heart rate. For DNA methylation association analysis, we find that two CpGs (cg16687447, cg06947206) upstream of PTEN were associated with platelet count. In conclusion, extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA, providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.Keywords: Adaptive potentials,
Extreme hypoxia environment,
DNA methylation,
Phenotype association,
Elite alpinists,
Mountaineering
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