Natural selection on EPAS1 ( HIF2α ) associated with low hemoglobin concentration in Tibetan highlanders

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200-3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of…

• NS
  National Science Foundation
• NE
  National Evolutionary Synthesis Center
• RS
  Royal Society
• NN
  National Natural Science Foundation of China

  Award: 30890031
• CA
  Chinese Academy of Sciences

  Award: KSCX2-YW-R
• NI
  National Institutes of Health
• BI
  Beijing Institute of Genomics, Chinese Academy of Sciences
• NH
  National Heart, Lung, and Blood Institute
• NC
  National Cancer Institute
• NI
  National Institute of General Medical Sciences
• NC
  National Center for Research Resources