What this means

EPAS1 codes for HIF-2-alpha, a transcription factor at the centre of the body's response to low oxygen. Tibetans living above 4,000 metres carry EPAS1 variants — likely inherited from Denisovan ancestors — that blunt the usual compensatory increase in red blood cell mass at altitude. Counterintuitively this is protective: very high haemoglobin at altitude causes chronic mountain sickness. The Tibetan-enriched variants let carriers function at altitude without that compensatory burden.

EPAS1 makes a protein that controls how your body responds to low oxygen. People living high in the Tibetan plateau carry a version of this gene — likely inherited from Denisovan ancestors tens of thousands of years ago — that stops the usual reaction of pumping out lots of extra red blood cells at altitude. It sounds counterintuitive, but very high red blood cell counts at altitude actually cause chronic mountain sickness. The Tibetan version lets people function at extreme altitude without that burden.

Caveats

• These variants are concentrated in Tibetan, Sherpa, and some neighbouring populations.
• Carrying the variant does not automatically mean better altitude performance.
• Acclimatisation and training matter enormously at altitude.
• Effect sizes outside the studied populations are not well characterised.

References

• Yi et al. — Sequencing of 50 human exomes reveals adaptation to high altitude (Science, 2010)
• Huerta-Sánchez et al. — Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA (Nature, 2014)