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Genes from Extinct Humans Helped Tibetans Survive in High Altitude

Jul 3, 2014 By Nathan Fortin Leave a Comment

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Tibetans living on the roof of the world can thank an extinct human relative for providing a gene that helps them adapt to the high altitude, a study suggests.

Past research has concluded that a particular gene helps people live in the thin air of the Tibetan plateau. Now scientists report that the Tibetan version of that gene is found in DNA from Denisovans, a poorly understood human relative more closely related to Neanderthals than modern people.

Denisovans are known only from fossils in a Siberian cave that are dated to at least about 50,000 years ago. Some of their DNA has also been found in other modern populations, indicating they interbred with ancient members of today’s human race long ago.

But the version of the high-altitude gene shared by Denisovans and Tibetans is found in virtually no other population today, researchers report in an article released Wednesday by the journal Nature.

The results show that as early members of today’s human species expanded outside of Africa and encountered new environments, they could call on their genetic legacies from other species, he said. That’s easier than waiting for a helpful genetic mutation to arise, he said.

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.”

David Reich, an expert on ancient DNA at Harvard Medical School, called the paper important and exciting in showing the gene came from an ancient human relative. But he said that relative could have been Neanderthals, who are also known to have contributed DNA to modern people.

Nielsen said the Tibetan gene variant doesn’t match any known Neanderthal DNA, but Reich said maybe scientists just haven’t yet found DNA from a Neanderthal who carried it.

 

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Filed Under: Tech & Science Tagged With: extinct, Extinct Human Gene, gene, high-altitude, Survive, Tibetans

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