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Zoological Research
Kunming Institute of Zoology, Chinese Academy of Sciences
ISSN: 2095-8137
Vol. 38, No. 3, 2017, pp. 163-170
Bioline Code: zr17021
Full paper language: English
Document type: Research Article
Document available free of charge

Zoological Research, Vol. 38, No. 3, 2017, pp. 163-170

 en EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production
Zheng, Wang-Shan; He, Yao-Xi; Cui, Chao-Ying; Ouzhuluobu; Dejiquzong; Peng, Yi; Bai, Cai-Juan; Duojizhuoma; Gonggalanzi; Bianba; Baimakangzhuo; Pan, Yong-Yue; Qula; Kangmin; Cirenyangji; Baimayangji; Guo, Wei; Yangla; Zhang, Hui; Zhang, Xiao-Ming; Guo, Yong-Bo; Xu, Shu-Hua; Chen, Hua; Zhao, Sheng-Guo; Cai, Yuan; Liu, Shi-Ming; Wu, Tian-Yi; Qi, Xue-Bin & Su, Bing

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.

Keywords
Tibetans; High altitude; Hypoxia; EP300; Genetic adaptation; Nitric oxide

 
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