Hypoxia: adapting to high altitude by mutating EPAS-1, the gene encoding HIF-2α.

Abstract Tissot van Patot, Martha C. and Max Gassman. Hypoxia: Adapting to high altitude by mutating EPAS-1, the gene encoding HIF-2α. High Alt. Med. Biol. 12:157–167, 2011.—Living at high altitude is demanding and thus drives adaptational mechanisms. The Tibetan population has had a longer evolutionary period to adapt to high altitude than other mountain populations such as Andeans. As a result, some Tibetans living at high altitudes do not show markedly elevated red blood cell production as compared to South American high altitude natives such as Quechuas or Aymaras, thereby avoiding high blood viscosity creating cardiovascular risk. Unexpectedly, the responsible mutation(s) reducing red blood cell production do not involve either the gene encoding the blood hormone erythropoietin (Epo), or the corresponding regulatory sequences flanking the Epo gene. Similarly, functional mutations in the hypoxia-inducible transcription factor 1α (HIF-1α) gene that represents the oxygen-dependent subunit of the HIF-1 h...