Gene Variant from Ancient Human Relative Helps Tibetans Survive at High Altitude

Tibetans survive at high altitudes due to a gene variant inherited from an ancient human cousin, a new study has found.

The study, conducted by University of California Berkeley researchers, shows that early humans interbred with an ancient species of humans called Denisovans.

"We have very clear evidence that this version of the gene came from Denisovans," said Rasmus Nielsen, UC Berkeley professor of integrative biology, lead author of the study. "This shows very clearly and directly that humans evolved and adapted to new environments by getting their genes from another species."

Denisovans were mysterious human relatives that went extinct some 40,000-50,000 years ago as did another human cousin - The Neanderthals.

Around four years ago, after another team of researchers analyzed 41,000-year-old tiny bone fragments, it was established that the DNA belonged to Denisovans.

Previous research had shown that a variant of EPAS1 gene variant has helped Tibetans survive at the roof of the world, one of the most inhospitable living conditions on earth. Oxygen at the Tibetan plateau is only about 60 percent of that at sea level.

The oxygen level is so low that other people without the gene variant develop thick blood and have higher risk of heart diseases.

The EPA S1 gene is associated with hemoglobin level in the blood. The gene is activated when the body detects a drop in oxygen levels in the blood. EPA S1 triggers the production of more hemoglobin.

At lower elevation, this increase in hemoglobin could boost athletic performance; but at high altitude, the gene could lead to several health problems.

Tibetans have a different version of the gene, one that helps release low amounts of hemoglobin. The variant helps avoid side-effects of living at such a high altitude.

Around 87 percent of Tibetans have the high-altitude version of EPA S1, compared to only 9 percent of Han Chinese, another group of humans that live at lower elevation and are closely related to Tibetans.

In the present study, researchers were looking for the source of the high-altitude EPA S1 gene variant. The team sequenced the gene in 40 Tibetans and 40 Han Chinese.

Researchers found that the variant was so unique that it could have come only from another human species - The Denisovans.  

Researchers said that early Homo sapiens, coming from Africa might have interbred with Denisovans on their way from Eurasia to China. These genes helped a tiny population survive severe conditions at the Tibetan plateau. The gene variant was passed down to subsequent generations in the people living in Tibet.

"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 in a news release. "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?"

The study is published in the journal Nature. It was funded by the State Key Development Program for Basic Research of China, U.S. National Institutes of Health and others.