Genetic evidence for high-altitude adaptation in Tibet.
Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.
Simonson
Tatum S
TS
Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Yang
Yingzhong
Y
Huff
Chad D
CD
Yun
Haixia
H
Qin
Ga
G
Witherspoon
David J
DJ
Bai
Zhenzhong
Z
Lorenzo
Felipe R
FR
Xing
Jinchuan
J
Jorde
Lynn B
LB
Prchal
Josef T
JT
Ge
RiLi
R
D000064:Acclimatization; D000531:Altitude; D044466:Asian People / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D016014:Linear Models; D008297:Male; D010100:Oxygen; D047493:PPAR alpha / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*; D012641:Selection, Genetic; D015398:Signal Transduction; D018609:Tibet
D006454:Hemoglobins; D051793:Hypoxia-Inducible Factor 1; D047493:PPAR alpha; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen