Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

Zhuoma Basang; Shixuan Zhang; La Yang; Deji Quzong; Yi Li; Yanyun Ma; Meng Hao; WeiLin Pu; Xiaoyu Liu; Hongjun Xie; Meng Liang; Jiucun Wang; Qiangba Danzeng

doi:10.1016/j.jgg.2021.05.015

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

J Genet Genomics. 2021 Oct 20;48(10):928-935. doi: 10.1016/j.jgg.2021.05.015. Epub 2021 Jul 6.

Authors

Zhuoma Basang¹, Shixuan Zhang¹, La Yang², Deji Quzong², Yi Li³, Yanyun Ma⁴, Meng Hao⁵, WeiLin Pu⁶, Xiaoyu Liu⁶, Hongjun Xie², Meng Liang⁵, Jiucun Wang⁷, Qiangba Danzeng⁸

Affiliations

¹ 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; Tibet University-Fudan University Joint Laboratory for Biodiversity and Global Change, Tibet University, 10 East Zangda Road, Lhasa, Tibet 850000, China.
² 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.
³ State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China; Institute for Six-sector Economy, Fudan University, Shanghai 200433, China.
⁴ Institute for Six-sector Economy, Fudan University, Shanghai 200433, China; Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.
⁵ Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.
⁶ State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China.
⁷ State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China; Tibet University-Fudan University Joint Laboratory for Biodiversity and Global Change, Tibet University, 10 East Zangda Road, Lhasa, Tibet 850000, China. Electronic address: jcwang@fudan.edu.cn.
⁸ 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. Electronic address: qiangba2021@163.com.

PMID: 34531147
DOI: 10.1016/j.jgg.2021.05.015

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 (P_adj < 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; DNA methylation; Elite alpinists; Extreme hypoxia environment; Mountaineering; Phenotype association.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation*