Genetic Adaptation of the Hypoxia-Inducible Factor Pathway to Oxygen Pressure among Eurasian Human Populations
文献类型：期刊论文
| 作者 | Ji LD1,2,3; Qiu YQ2,4; Xu J1,2,5; Irwin DM1,6,7; Tam SC8; Tang NLS[*]2,4,9,10; Zhang YP[*]1,2,11 |
| 刊名 | MOLECULAR BIOLOGY AND EVOLUTION
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| 出版日期 | 2012 |
| 卷号 | 29期号:11页码:3359-3370 |
| 关键词 | adaptive evolution human genetic variation oxygen pressure hypoxia hypoxia-inducible factor pathway Eurasian populations |
| 通讯作者 | nelsontang@cuhk.edu.hk ; zhangyp@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | Research into the mechanisms of human adaptation to the hypoxic environment of high altitude is of great interest to the fields of human physiology and clinical medicine. Recently, the gene EGLN1, from the hypoxia-inducible factor (HIF) pathway, was identified as being involved in the hypoxic adaptation of highland Andeans and Tibetans. Both highland Andeans and Tibetans have adapted to an extremely hypoxic habitat and less attention has been paid to populations living in normoxic conditions at sea level and mild-hypoxic environments of moderate altitude, thus, whether a common adaptive mechanism exists in response to quantitative variations of environmental oxygen pressure over a wide range of residing altitudes is unknown. Here, we first performed a genome-wide association study of 35 populations from the Human Genome Diversity-CEPH Panel who dwell at sea level to moderate altitude in Eurasia (N = 691; 0-2,500 m) to identify the genetic adaptation profile of normoxic and mild-hypoxic inhabitants. In addition, we systematically compared the results from the present study to six previously published genome-wide scans of highland Andeans and Tibetans to identify shared adaptive signals in response to quantitative variations of oxygen pressure. For normoxic and mild-hypoxic populations, the strongest adaptive signal came from the mu opioid receptor-encoding gene (OPRM1, 2.54 x 10(-9)), which has been implicated in the stimulation of respiration, while in the systematic survey the EGLN1-DISC1 locus was identified in all studies. A replication study performed with highland Tibetans (N = 733) and sea level Han Chinese (N = 748) confirmed the association between altitude and SNP allele frequencies in OPRM1 (in Tibetans only, P < 0.01) and in EGLN1-DISC1 (in Tibetans and Han Chinese, P < 0.01). Taken together, identification of the OPRM1 gene suggests that cardiopulmonary adaptation mechanisms are important and should be a focus in future studies of hypoxia adaptation. Furthermore, the identification of the EGLN1 gene from the HIF pathway suggests a common adaptive mechanism for Eurasian human populations residing at different altitudes with different oxygen pressures. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by grants from the National Basic Research Program of China (973 Program, 2007CB411600), the National Natural Science Foundation of China, and Bureau of Science and Technology of Yunnan Province. This research was done in State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences and Department of Chemical Pathology, The Chinese University of Hong Kong. |
| 语种 | 英语 |
| WOS记录号 | WOS:000310167700011 |
| 公开日期 | 2013-04-09 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7312]  |
| 专题 | 昆明动物研究所_分子进化基因组学 昆明动物研究所_遗传资源与进化国家重点实验室 |
| 作者单位 | 1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China 3.Institute of Biochemistry, School of Medicine, Ningbo University, Ningbo, China 4.Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China 5.Institute of Public Health, School of Medicine, Ningbo University, Ningbo, China 6.Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 7.Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada 8.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China 9.Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China 10.ShenZhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China |
| 推荐引用方式 GB/T 7714 | Ji LD,Qiu YQ,Xu J,et al. Genetic Adaptation of the Hypoxia-Inducible Factor Pathway to Oxygen Pressure among Eurasian Human Populations[J]. MOLECULAR BIOLOGY AND EVOLUTION,2012,29(11):3359-3370. |
| APA | Ji LD.,Qiu YQ.,Xu J.,Irwin DM.,Tam SC.,...&Zhang YP[*].(2012).Genetic Adaptation of the Hypoxia-Inducible Factor Pathway to Oxygen Pressure among Eurasian Human Populations.MOLECULAR BIOLOGY AND EVOLUTION,29(11),3359-3370. |
| MLA | Ji LD,et al."Genetic Adaptation of the Hypoxia-Inducible Factor Pathway to Oxygen Pressure among Eurasian Human Populations".MOLECULAR BIOLOGY AND EVOLUTION 29.11(2012):3359-3370. |
入库方式： OAI收割
来源：昆明动物研究所
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