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Extinct human cousin gave Tibetans advantage at high elevation

Denisovan gene helped Tibetans adapt to low oxygen at high altitudes.

Tibetans gained the ability to adapt to high altitudes due to a gene they acquired when their ancestors bred with a species of human they subsequently helped push to extinction, according to a new report by scientists at the University of California, Berkeley.

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An unusual variant of a gene involved in the regulation of the body’s production of hemoglobin- the molecule responsible for carrying oxygen in the blood- became widespread in Tibetans after moving onto the high-altitude plateau several thousand years ago. This variant permitted them to survive despite low oxygen levels at elevations of 15,000 feet or more, whereas most people develop thick blood at high altitudes, which leads to cardiovascular problems.

“We have very clear evidence that this version of the gene came from Denisovans,” a mystifying human relative that went extinct approximately 40,000-50,000 years ago, around the same time as the well known Neanderthals, under pressure from modern humans, said principal author Rasmus Nielsen, UC Berkeley professor of integrative biology. “This shows very clearly and directly that humans evolved and adapted to new environments by getting their genes from another species.”

He continued to say that this is the first time a gene from another species of human has been shown explicitly to help modern humans adapt to their environment.

Nielsen, along with his colleagues at BGI-Shenzen in China reported their findings on July 2nd in advance of their publication in the journal Nature.

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The gene, called EPAS1, activates when oxygen levels in the blood drop, triggering production of more hemoglobin. The gene is also know as the superathlete gene because at low elevations, some variants of it help athletes quickly boost hemoglobin and therefore the oxygen-carrying capacity of their blood, increasing their endurance. At high altitude, however, the common variants of the gene increase hemoglobin and its carrier, red blood cells, too much, increasing the thickness of the blood, leading to hypertension and heart attacks, as well as low-birth weight babies and an increase in infant mortality. The variant or allele that is found in Tibetans raises hemoglobin and red blood cells only a little at high elevation, avoiding the negative side-effects that are seen in most people who relocate to elevations of more than 13,000 feet.

“We found part of the EPAS1 gene in Tibetans is almost identical to the gene in Denisovans and very different from all other humans,” Nielsen said. “We can do a statistical analysis to show that this must have come from Denisovans. There is no other way of explaining the data.”

People of Tibet: Fotopedia
People of Tibet: Fotopedia

Harsh Conditions on Tibetan Plateau

The group of researchers first reported the prevalence of a high-altitude version of EPAS1 in Tibetans back in 2010, based on sequencing the genomes of numerous Han Chinese and Tibetans. Nielsen and his colleagues instigated an argument that this was due to natural selection to adapt approximately 40 percent lower oxygen levels on the Tibetan plateau. That is, people lacking the variant died before reproducing at an increased rate than those with it. About 87 percent of Tibetans now possess the high-altitude version, compared to only 9 percent of Han Chinese, who have the same common ancestor as Tibetans.

Subsequently, Nielsen and his colleagues sequenced the EPAS1 gene in a further 40 Tibetans and 40 Han Chinese. The data revealed that the high-altitude variant of EPAS1 is so unusual that it could have only originated from Denisovans. Apart from its low frequency in Han Chinese, it is not present in any other known humans, not even Melanesians, who share nearly 5 percent of their genomes with the Denisovan people. A high quality sequence of the Denisovan genome was published in 2012.

Nielsen sketched out a possible scenario leading to this finding: modern humans coming out of Africa interbred with Denisovan populations in Eurasia as they passed through the area into China, and their descendants still retain a small percentage, perhaps as small as 0.1 percent, Denisovan DNA. The group that invaded China ultimately split, with one population relocating to Tibet and the other, now known as Han Chinese, domination the lower elevations.

Nielsen and his colleagues were analyzing other genomes to determine the time in which the Denisovan interbreeding occurred; it has been found that this probably happened over a rather short period of time.

“There might be many other species from which we also got DNA, but we don’t know because we don’t have the genomes,” Nielsen said. “The only reason we can say that this bit of DNA is Denisovan is because of this lucky accident of sequencing DNA from a little bone found in a cave in Siberia. We found the Denisovan species at the DNA level, but how many other species are out there that we haven’t sequenced?”

 

Contributing Source: University of California- Berkeley

Header Image Source: WikiPedia

 

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Mark Milligan
Mark Milligan
Mark Milligan is multi-award-winning journalist and the Managing Editor at HeritageDaily. His background is in archaeology and computer science, having written over 7,500 articles across several online publications. Mark is a member of the Association of British Science Writers (ABSW), the World Federation of Science Journalists, and in 2023 was the recipient of the British Citizen Award for Education, the BCA Medal of Honour, and the UK Prime Minister's Points of Light Award.
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