A variant of the gene EGLN1 is a key contributor to the ability of Tibetan Highlanders to live at extremely high elevations, reports a paper published online this week in Nature Genetics. This variant helps Tibetan Highlanders avoid producing too many red blood cells in response to low oxygen environments, preventing the life-threatening complications that occur in non-adapted individuals.
The Tibetan Plateau is the highest in the world, with an average elevation of over 4500 meters (approximately 3 miles). The level of oxygen on the plateau is only two-thirds of that at sea level. In most non-adapted individuals, exposure to low oxygen levels leads to excessive production of red blood cells, which causes thickening of the blood. This impairs blood flow and oxygen delivery, and can be fatal.
Josef Prchal and colleagues studied native Tibetan Highlanders, living in the US, to determine the genetic basis for their adaptation. A high-resolution analysis of candidate genes enabled them to find a new variant in EGLN1 that is present in approximately 85% of Tibetans, compared to only 0.8% of non-Tibetans. The authors isolated cells from the blood of both Tibetans and non-Tibetans, and found that the Tibetan form of the protein encoded by EGLN1 (PHD2) was more efficient at blocking red blood cell production, but only at low oxygen concentrations.