Tibetans inherited a genetic adaptation to high altitudes from an extinct group of human relatives called Denisovans, a new study finds.
Researchers have known for years that Tibetans carry a genetic variant in the EPAS1 gene that allows them to survive at extreme altitudes where oxygen is scarce. But how that variant arose has been mysterious. Now researchers report July 2 in Nature that the high-altitude version of EPAS1 almost certainly came from Denisovans or from a related group of extinct humans.
The case is the most compelling yet that humans picked up helpful genetic variants through interbreeding with hominids that have since gone extinct, says Anna Di Rienzo, a human population geneticist at the University of Chicago, who was not involved with the research. Human evolution probably contains many other examples of people inheriting advantageous mutations by interbreeding with groups that have already adapted to the environment, she says.
At an elevation of more than 4,000 meters, the Tibetan Plateau has oxygen levels that are 40 percent lower than those at sea level. The EPAS1 variant helps Tibetans cope with constant oxygen deprivation, an extreme stress on the body especially during pregnancy. The genetic variant was probably important in allowing people to settle the plateau, says Rasmus Nielsen, a computational biologist and evolutionary geneticist at the University of California, Berkeley, who led the work.
Nielsen and his colleagues had previously tried unsuccessfully to pinpoint when the helpful mutation arose. The researchers compared a stretch of DNA surrounding EPAS1 that is 32,700 DNA letters long from 40 Tibetans and 40 Han Chinese, who are close genetic relatives of Tibetans. A distinctive pattern of single DNA letter changes, or SNPs, set the Tibetans apart from other groups.
The signature appeared in two Han Chinese people but, so far, hasn’t been found in any other modern human groups. Nielsen’s team also compared the DNA to that of Neandertals, but the string of DNA didn’t seem to come from them either. “So we just put it aside because we couldn’t make sense of the data,” Nielsen says.
But then in 2010, scientists announced that a 41,000 year-old finger bone found in Siberia was from a previously unknown group of extinct people. The people were dubbed Denisovans after the cave in which the fossil was found. When the Denisovan genome became available (SN: 9/22/12, p. 5), Nielsen and his colleagues decided to compare the distinctive Tibetan signature to the Denisovan DNA. It was a long shot, but to the researcher’s surprise, the Denisovan DNA held an exact match to a five-SNP signature that all Tibetans have. In fact, Denisovans shared 15 of 20 Tibetan SNPs, the team discovered.
Computer simulations of scenarios under which the two groups could share DNA indicated that the most likely explanation for the similarity is that Tibetans inherited the chunk of DNA containing the helpful EPAS1 variant as well as the SNPs from Denisovans. Previously, Denisovans were known to have passed a small amount of their genetic heritage to Melanesians and a few other East Asian groups, but the study is among the first to indicate that the genetic legacy could play a role in modern human evolution.
Other researchers agree that Nielsen’s group presents convincing evidence that the high-altitude version of EPAS1 came from Denisovans or a related extinct group.
“They really nailed it that it came from archaic humans,” says Pontus Skoglund, a population geneticist at Harvard Medical School. But he’s not convinced Denisovans passed the adaptation directly to Tibetans. Because Denisovans and Neandertals are known to have interbred and present-day Tibetans carry a fair amount of Neandertal ancestry, Skoglund thinks “there’s still a little wiggle room for it to have come from Neandertals.”
Tibetans have lived on the plateau for at least 10,000 years and they probably already carried the adaptation when they migrated there, says Mark Aldenderfer, an archaeologist at the University of California, Merced. Tibetans probably inherited the adaptation from descendants of Denisovans, he says. But it is not clear where or why the Denisovans or their descendants picked up and kept that mutation, since there are no mountain ranges around Siberia that are high enough to require this sort of adaptation, he says.