Tibetans are comfortable at high altitudes where the air is thin. Now it seems a gene variant that gives them an edge over other people did not evolve in modern humans. It comes from an extinct species of human called the Denisovans.
Living on the roof of the world is hard. The air there carries less oxygen, making it harder to breathe and causing a host of problems. For instance, it is harder to conceive high up in the mountains. But Tibetans manage just fine.
Studies have linked their altitude adaptation to several genes including EPAS1, part of the system that helps the body react to low levels of oxygen. The Tibetan version of EPAS1 came from ancestors of the Nepalese Sherpa people and spread rapidly through the population 30,000 years ago, suggesting it is beneficial.
Now Rasmus Nielsen of the University of California, Berkeley, and his colleagues have compared Tibetan genomes with populations from around the world. No other modern group carries the Tibetan variant of EPAS1.
Good for the blood
But they found the same gene variant in the genome of a Denisovan, an extinct species of human known only from a cave in the Altai mountains in east-central Asia.
“The study shows that one of the most spectacular cases of [genetic] adaptation in humans has its roots in Denisovans,” says Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “It is very satisfying to see that gene flow from Denisovans, an extinct group of archaic humans that we discovered only four years ago, is now found to have had important consequences for people living today.”
The Tibetan EPAS1 probably got there by interbreeding, but more evidence is needed to confirm which archaic humans were the source, says David Reich of Harvard Medical School in Boston. “There is no proof in the paper that the origin of the [DNA] is Denisovan.” He says it could just as easily have come from Neanderthals, whose EPAS1 looks similar to the Tibetans’. That might make more sense as they were common on mainland Asia, whereas the Denisovan heartland seems to have been in South-East Asia.
It is still unclear how the modified EPAS1 gene helps Tibetans survive 4000 metres above sea level. It seems to cut the number of red blood cells, which carry oxygen, being made. That is odd: most people make more of these cells when they travel to high altitudes, to carry more oxygen. But they thicken the blood, possibly making strokes more likely. Nielsen thinks that, by thinning the blood, the Tibetan gene may help lower this risk.
Denisovans are one of at least two extinct hominin species that humans mated with, the other being Neanderthals. Many of us carry bits of DNA from these other species.
The new finding adds to the evidence that this interbreeding had significant effects on our evolution. For instance, Neanderthal DNA is particularly common in genes relating to keratin, a protein found in hair, skin and nails. Another Neanderthal gene found in modern Eurasians may increase the risk of type 2 diabetes.
Humans interbred with Neanderthals soon after moving out of Africa, when we were ill-equipped to cope with Eurasian diseases. However Neanderthals had been hanging out in Europe and Asia for much longer, so their immune systems had adapted. There is evidence that humans snagged some of the Neanderthals’ immunity genes when the two mated, perhaps helping us to spread across the planet.
Journal reference: Nature, DOI: 10.1038/nature13408