The adaptation of Tibetans to high-altitude environments has been studied extensively. However, the direct assessment of evolutionary adaptation, i.e., the reproductive fitness of Tibetans and its genetic basis, remains elusive. Here, we conduct systematic phenotyping and genome-wide association analysis of 2,252 mother-newborn pairs of indigenous Tibetans, covering 12 reproductive traits and 76 maternal physiological traits. Compared with the lowland immigrants living at high altitudes, indigenous Tibetans show better reproductive outcomes, reflected by their lower abortion rate, higher birth weight, and better fetal development. The results of genome-wide association analyses indicate a polygenic adaptation of reproduction in Tibetans, attributed to the genomic backgrounds of both the mothers and the newborns. Furthermore, the EPAS1-edited mice display higher reproductive fitness under chronic hypoxia, mirroring the situation in Tibetans. Collectively, these results shed new light on the phenotypic pattern and the genetic mechanism of human reproductive fitness in extreme environments. Publication: Current Biology, Volume 33, Issue 19, 9 October 2023, Pages 4037-4051.e5 http://dx.doi.org/10.1016/j.cub.2023.08.021
Author: Yaoxi He,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;Yongbo Guo,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China;Wangshan Zheng,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China;Tian Yue,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China;Hui Zhang,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China;Bin Wang,Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China;Zhanying Feng,CEMS, NCMIS, MDIS, Academy of Mathematics & Systems Science, Chinese Academy of Sciences, Beijing 100080, China,Ouzhuluobu,Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China,High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa 850000, China;Chaoying Cui,Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China,High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa 850000, China;Kai Liu,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;Bin Zhou,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China, Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China;Xuerui Zeng,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China;Liya Li,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Tianyun Wang Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;Yong Wang,CEMS, NCMIS, MDIS, Academy of Mathematics & Systems Science, Chinese Academy of Sciences, Beijing 100080, China,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China;,Chao Zhang,Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China;Shuhua Xu,State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China,Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai 201203, China;Xuebin Qi,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China,State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China;Bing Su,State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
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