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

被引：17

作者：

Guo, Yong-Bo ^{[1
,2
]}

He, Yao-Xi ^{[2
,4
]}

Cui, Chao-Ying ^{[3
]}

Ouzhuluobu ^{[3
]}

Baimakangzhuo ^{[3
]}

Duojizhuoma ^{[3
]}

Dejiquzong ^{[3
]}

Bianba ^{[3
]}

Peng, Yi ^{[2
]}

Bai, Cai-juan ^{[3
]}

Gonggalanzi ^{[3
]}

Pan, Yong-Yue ^{[3
]}

Qula ^{[3
]}

Kangmin ^{[3
]}

Cirenyangji ^{[3
]}

Baimayangji ^{[3
]}

Guo, Wei ^{[3
]}

Yangla ^{[3
]}

Zhang, Hui ^{[2
]}

Zhang, Xiao-Ming ^{[2
]}

Zheng, Wang-Shan ^{[1
,2
]}

Xu, Shu-Hua ^{[5
,8
,9
]}

Chen, Hua ^{[6
]}

Zhao, Sheng-Guo ^{[1
]}

Gai, Yuan ^{[1
]}

Liu, Shi-Ming ^{[7
]}

Wu, Tiari-Yi ^{[7
]}

Qi, Xue-Bin ^{[2
]}

Su, Bing ^{[2
]}

机构：

[1] Gansu Agr Univ, Coll Anim Sci & Technol, Lanzhou 730070, Gansu, Peoples R China

[2] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China

[3] Tibetan Univ, Sch Med, High Altitude Med Res Ctr, Lhasa Tibet 850000, Peoples R China

[4] Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China

[5] Chinese Acad Sci, Key Lab Computat Biol, Max Planck Independent Res Grp Populat Genom, CAS MPG Partner Inst Computat Biol PICB,Shanghai, Shanghai 200031, Peoples R China

[6] Chinese Acad Sci, Ctr Computat Genom, Beijing Inst Genom, Beijing 100101, Peoples R China

[7] High Altitude Med Res Inst, Natl Key Lab High Altitude Med, Xining 810012, Qinghai, Peoples R China

[8] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China

[9] Collaborat Innovat Ctr Genet & Dev, Shanghai 200438, Peoples R China

来源：

ZOOLOGICAL RESEARCH | 2017年 / 38卷 / 03期

基金：

中国国家自然科学基金;

关键词：

GCH1; Hemoglobin; Hypoxia adaptation; Nitric oxide; Oxygen saturation; Positive selection; Tibetan;

D O I：

10.24272/j.issn.2095-8137.2017.037

中图分类号：

Q95 [动物学];

学科分类号：

071002 ;

摘要：

Tibetans are well 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 GCH1 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.

引用

页码：155 / 162

页数：8

共 36 条

[1] 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels - Effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling [J].

Antoniades, Charalambos ;

Shirodaria, Cheerag ;

Warrick, Nicholas ;

Cai, Shijie ;

de Bono, Joseph ;

Lee, Justin ;

Leeson, Paul ;

Neubauer, Stefan ;

Ratnatunga, Chandi ;

Pillai, Ravi ;

Refsum, Helga ;

Channon, Keith M. .

CIRCULATION, 2006, 114 (11) :1193-1201

[2] Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia [J].

Beall, CM .

INTEGRATIVE AND COMPARATIVE BIOLOGY, 2006, 46 (01) :18-24

[3]

Beall CM, 1997, AM J PHYS ANTHROPOL, V104, P427, DOI 10.1002/(SICI)1096-8644(199712)104:4<427::AID-AJPA1>3.0.CO

[4]

2-P

[5] Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders [J].

Beall, Cynthia M. ;

Cavalleri, Gianpiero L. ;

Deng, Libin ;

Elston, Robert C. ;

Gao, Yang ;

Knight, Jo ;

Li, Chaohua ;

Li, Jiang Chuan ;

Liang, Yu ;

McCormack, Mark ;

Montgomery, Hugh E. ;

Pan, Hao ;

Robbins, Peter A. ;

Shianna, Kevin V. ;

Tam, Siu Cheung ;

Tsering, Ngodrop ;

Veeramah, Krishna R. ;

Wang, Wei ;

Wangdui, Puchung ;

Weale, Michael E. ;

Xu, Yaomin ;

Xu, Zhe ;

Yang, Ling ;

Zaman, M. Justin ;

Zeng, Changqing ;

Zhang, Li ;

Zhang, Xianglong ;

Zhaxi, Pingcuo ;

Zheng, Yong Tang .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (25) :11459-11464

[6] Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data [J].

Bigham, Abigail ;

Bauchet, Marc ;

Pinto, Dalila ;

Mao, Xianyun ;

Akey, Joshua M. ;

Mei, Rui ;

Scherer, Stephen W. ;

Julian, Colleen G. ;

Wilson, Megan J. ;

Herraez, David Lopez ;

Brutsaert, Tom ;

Parra, Esteban J. ;

Moore, Lorna G. ;

Shriver, Mark D. .

PLOS GENETICS, 2010, 6 (09)

[7] Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP plus [J].

Davydov, Eugene V. ;

Goode, David L. ;

Sirota, Marina ;

Cooper, Gregory M. ;

Sidow, Arend ;

Batzoglou, Serafim .

PLOS COMPUTATIONAL BIOLOGY, 2010, 6 (12)

[8] ChromHMM: automating chromatin-state discovery and characterization [J].

Ernst, Jason ;

Kellis, Manolis .

NATURE METHODS, 2012, 9 (03) :215-216

[9] Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans [J].

Erzurum, S. C. ;

Ghosh, S. ;

Janocha, A. J. ;

Xu, W. ;

Bauer, S. ;

Bryan, N. S. ;

Tejero, J. ;

Hemann, C. ;

Hille, R. ;

Stuehr, D. J. ;

Feelisch, M. ;

Beall, C. M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (45) :17593-17598

[10] 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT) [J].

Galie, Nazzareno ;

Humbert, Marc ;

Vachiery, Jean-Luc ;

Gibbs, Simon ;

Lang, Irene ;

Torbicki, Adam ;

Simonneau, Gerald ;

Peacock, Andrew ;

Noordegraaf, Anton Vonk ;

Beghetti, Maurice ;

Ghofrani, Ardeschir ;

Gomez Sanchez, Miguel Angel ;

Hansmann, Georg ;

Klepetko, Walter ;

Lancellotti, Patrizio ;

Matucci, Marco ;

McDonagh, Theresa ;

Pierard, Luc A. ;

Trindade, Pedro T. ;

Zompatori, Maurizio ;

Hoeper, Marius .

EUROPEAN HEART JOURNAL, 2016, 37 (01) :67-+

← 1 2 3 4 →