Scientists have long wondered how Tibetans conquered the threat of hypoxia in this harsh environment. Hypoxia is a lower than normal level of oxygen in the blood. A super athlete gene that helps Tibetans breathe easy at high altitudes was inherited from an ancient species of human.
That’s the conclusion of a new study, which finds that the gene variant came from people known as Denisovans, who went extinct soon after they mated with the ancestors of Europeans and Asians about 40,000 years ago. This is the first time a version of a gene acquired from interbreeding with another type of human has been shown to help modern humans adapt to their environment. Researchers have long wondered how Tibetans live and work at altitudes above 4000 meters, where the limited supply of oxygen makes most people sick.
The potentially fatal condition is characterized by severe shortness of breath with headache, insomnia, fluid retention and cough, and it can occur at altitudes above 8,000 feet. Recent studies on the genetics of Tibetans identified a hypoxia pathway gene, EPAS1, which may have been linked to differences in hemoglobin concentration at high altitudes. To make their findings the research team re-sequenced the region around EPAS1 in 40 Tibetan and 40 Han individuals.
In the new study, scientists collected blood samples from 40 Tibetans and sequenced more than 30,000 nucleotides on a segment of DNA containing EPAS1, the gene that makes Tibetans so well-suited for life at high altitude. Then the scientists compared that sequence with those of 1,000 individuals representing the 26 human populations in the Human Genome Diversity Panel. They found the high-altitude gene in only 2 of the 40 Han Chinese people in the panel and no one else.
“Natural selection by itself could not explain that pattern,” said Rasmus Nielsen, a computational biologist at UC Berkeley and an author of the study. “The DNA sequence was too different from anything else we saw in other populations.”
So they investigated whether the gene might have been imported from extinct Neanderthals or Denisovans, and, bingo, they found a match.
Although most Han Chinese and other groups lost the Denisovans’ version of the EPAS1 gene because it wasn’t particularly beneficial, Tibetans who settled on the high-altitude Tibetan plateau retained it because it helped them adapt to life there, the team reports online. The gene variant was favored by natural selection, so it spread rapidly to many Tibetans.
A few Han Chinese—perhaps 1% to 2%—still carry the Denisovan version of the EPAS1 gene today because the interbreeding took place when the ancestors of Tibetans and Chinese were still part of one group some 40,000 years ago. But the gene was later lost in most Chinese or the Han Chinese may have acquired it more recently from interbreeding with Tibetans, Nielsen says.
Although previous studies had identified the importance of EPAS1, scientists still don’t know exactly what the gene does. They know only that it leads to lower levels of hemoglobin, the oxygen-toting protein in blood, in Tibetans who live at high altitude compared with people from low elevations who have acclimatized.
But one thing is now clear: They owe their extraordinary fitness to a rogue gene introduced into the human genome from their long-lost cousins.
Either way, what is most interesting, Nielsen says, is that the results show that mating with other groups was an important source of beneficial genes in human evolution. “Modern humans didn’t wait for new mutations to adapt to a new environment,” he says. “They could pick up adaptive traits by interbreeding.”
The discovery is the second case in which modern humans have acquired a trait from archaic humans, notes paleo geneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, whose team discovered the Denisovan people. Earlier this year, another team showed that Mayans, in particular, have inherited a gene variant from Neandertals that increases the risk for diabetes.
The ultimate irony, Nielsen notes is that, once we got this beneficial gene, we never returned the favor. Instead, we may have helped drive the Denisovans extinct.