Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

TLDR

High‑altitude populations have evolved physiological adaptations, yet the genetic basis of these changes remains unclear. The study aimed to identify gene regions contributing to high‑altitude adaptation in Tibetans and to outline future functional investigations. The authors performed a genome‑wide scan of nucleotide polymorphisms among Tibetans, Han Chinese, and Japanese, and conducted exome‑wide analyses of coding regions to detect selection signals. Both studies identified EPAS1 (HIF‑2α) as a key gene linked to red‑blood‑cell regulation, and also highlighted hemoglobin genes and two loci associated with low hemoglobin levels in Tibetans.

Abstract

No Genetic Vertigo Peoples living in high altitudes have adapted to their situation (see the Perspective by Storz ). To identify gene regions that might have contributed to high-altitude adaptation in Tibetans, Simonson et al. (p. 72 , published online 13 May) conducted a genome scan of nucleotide polymorphism comparing Tibetans, Han Chinese, and Japanese, while Yi et al. (p. 75 ) performed comparable analyses on the coding regions of all genes—their exomes. Both studies converged on a gene, endothelial Per-Arnt-Sim domain protein 1 (also known as hypoxia-inducible factor 2 α), which has been linked to the regulation of red blood cell production. Other genes identified that were potentially under selection included adult and fetal hemoglobin and two functional candidate loci that were correlated with low hemoglobin concentration in Tibetans. Future detailed functional studies will now be required to examine the mechanistic underpinnings of physiological adaptation to high altitudes.