EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production |
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| Authors: | Wang-Shan Zheng Yao-Xi He Chao-Ying Cui Ouzhuluobu Dejiquzong Yi Peng Cai-Juan Bai Duojizhuoma Gonggalanzi Bianba Baimakangzhuo Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei Guo Yangla Hui Zhang Xiao-Ming Zhang Yong-Bo Guo Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su |
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| Institution: | 1. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou Gansu 730070, China;State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;2. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming Yunnan 650204, China;3. High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa Tibet 850000, China;4. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;5. Chinese Academy of Sciences Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, China;Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China;6. Center for Computational Genomics, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;7. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou Gansu 730070, China;8. National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining Qinghai 810012, China |
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| Abstract: | The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway,as suggested by earlier studies.To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300),we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans.The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans,with a group of variants showing allelic divergence between Tibetans and lowland reference populations,including Han Chinese,Europeans,and Africans.Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation.More importantly,genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration.Collectively,we propose that EP300 harbors adaptive variants in Tibetans,which might contribute to high-altitude adaptation through regulating NO production. |
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| Keywords: | Tibetans High altitude Hypoxia EP300 Genetic adaptation Nitric oxide |
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