Andean and Tibetan patterns of adaptation to high altitude.
OBJECTIVE
High-altitude hypoxia, or decreased oxygen levels caused by low barometric pressure, challenges the ability of humans to live and reproduce. Despite these challenges, human populations have lived on the Andean Altiplano and the Tibetan Plateau for millennia and exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. We and others have identified natural selection candidate genes and gene regions for these adaptations using dense genome scan data. One gene previously known to be important in cellular oxygen sensing, egl nine homolog 1 (EGLN1), shows evidence of positive selection in both Tibetans and Andeans. Interestingly, the pattern of variation for this gene differs between the two populations. Continued research among Tibetan populations has identified statistical associations between hemoglobin concentration and single nucleotide polymorphism (SNP) genotype at EGLN1 and a second gene, endothelial PAS domain protein 1 (EPAS1).


METHODS
To measure for the effects of EGLN1 and EPAS1 altitude genotypes on hemoglobin concentration among Andean highlanders, we performed a multiple linear regression analysis of 10 candidate SNPs in or near these two genes.


RESULTS
Our analysis did not identify significant associations between EPAS1 or EGLN1 SNP genotypes and hemoglobin concentration in Andeans.


CONCLUSIONS
These results contribute to our understanding of the unique set of adaptations developed in different highland groups to the hypoxia of high altitude. Overall, the results provide key insights into the patterns of genetic adaptation to high altitude in Andean and Tibetan populations.
Department of Anthropology, University of Michigan, Ann Arbor, Michigan.
Abigail W
AW
Bigham
Megan J
MJ
Wilson
Colleen G
CG
Julian
Melisa
M
Kiyamu
Enrique
E
Vargas
Fabiola
F
Leon-Velarde
Maria
M
Rivera-Chira
Carmelo
C
Rodriquez
Vaughn A
VA
Browne
Esteban
E
Parra
Tom D
TD
Brutsaert
Lorna G
LG
Moore
Mark D
MD
Shriver
D000064:Acclimatization; D000222:Adaptation, Physiological; D000531:Altitude; D044466:Asian People; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007199:Indians, South American; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013020:South America; D018609:Tibet
D006454:Hemoglobins