GCH1 plays a role in the high-altitude adaptation of Tibetans  

作　　者：Yong-Bo Guo Yao-Xi He Chao-Ying Cui Ouzhuluobu Baimakangzhuo Duojizhuoma Dejiquzong Bianba Yi Peng Cai-juan Bai Gonggalanzi Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei Guo Yangla Hui Zhang Xiao-Ming Zhang Wang-Shan Zheng Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su 

机构地区：[1]College of Animal Science and Technology, Gansu Agricultural University, Lanzhou Gansu 730070, China [2]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China [3]High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa Tibet 850000, China [4]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming Yunnan 650204, 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 (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [6]Center for Computational Genomics, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [7]National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining Qinghai 810012, China [8]School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, China [9]Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China

出　　处：《Zoological Research》2017年第3期155-162,共8页动物学研究（英文）

基　　金：supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000);the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou.,31501013 to HZ and 31360032 to CC);the National 973 program(2012CB518202 to TW);the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04);the Zhufeng Scholar Program of Tibetan University

摘　　要：Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyclohydrolase I）, involved in maintaining nitric oxide synthetase （NOS） function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans Combined with previously published data, we demonstrated many GCHI variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyclohydrolase I）, involved in maintaining nitric oxide synthetase （NOS） function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans Combined with previously published data, we demonstrated many GCHI variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.

关 键 词：GCH1 Positive selection TibetanHypoxia adaptation Nitric oxide HemoglobinOxygen saturation 

分 类 号：Q494[生物学—生理学]