Tibetans Got Their High-Altitude Gene Mixing With Archaic Humans

Jul 02, 2014 1:00 pm ET

July 2 (Bloomberg) -- Tibetans, who thrive in an oxygen- scarce, high-altitude environment that leaves most gasping for breath, may have inherited their ability to adapt from an ancient human ancestor discovered just four years ago.

Earlier studies identified a version of a gene called EPAS1 as being responsible to Tibetans’ ability to adjust to their environment 4,000 meters (13,000 feet) above sea level. An analysis of the variant, which isn’t found in other peoples, showed it in the remains of a Denisovan, the name for a species of human that lived about 41,000 years ago.

The findings, reported today in the journal Nature, suggest that interbreeding between modern humans and Denisovans provided the right genetic ingredients to enable their Tibetan descendants to thrive on the world’s highest plateau. In a broader sense, they also point to interbreeding between humans and other hominins as a key to survival in new environments.

“Perhaps that process of adaptive introgression, of getting genes from other species, might be more important in evolution than previously thought,” said Rasmus Nielsen, a professor at the University of California at Berkeley and one of the study’s authors.

The Denisovans, a human species distinct from Neanderthals and modern humans, could have interbred with the ancestors of Tibetans before they migrated upwards, making the adaptations an essential advantage, Nielsen said.

Oxygen Regulator

The study focused on the EPAS1 gene because it regulates levels of oxygen-carrying hemoglobin. In most people, the gene causes the body to produce more hemoglobin when less oxygen is available. At high altitudes, it can go too far. Thickened blood can cause heart problems, hypertension and higher infant mortality.

The variation carried by Tibetans only raises hemoglobin production slightly, leading to a distinct survival advantage. The same high-altitude friendly variation was present in the genome sequenced from a single finger bone found in the Denisova Cave in southern Siberia. DNA sequencing in 2010 found that bone to be distinct from both Neanderthals and humans, which also inhabited the cave at different times. The full Denisovan genome was sequenced in 2012.

Studies have found humans probably interbred with Neanderthals and Denisovans before they became extinct. About 2 to 4 percent of human DNA today is made up of Neanderthal genes, according to research published earlier this year. Research has suggested the interbreeding may have conferred advantages enabling humans to survive in non-African environments.

Adaptive Introgression

The Tibetan adaptation strengthens the argument for adaptive introgression, in which advantageous genes are absorbed from existing populations, said Anna Di Rienzo, a professor of human genetics at the University of Chicago who has also researched the origin of the Tibetans genetic variation.

“It’s one of the most clear-cut cases of adaptive introgression with archaic humans,” Di Rienzo said in an interview. “It’s clearly a very good case where we understand a lot about what’s going on with this adaptation.”

The single gene variation being present doesn’t tell much about how or when the interbreeding happened, Di Rienzo said. It’s possible that there was more interbreeding with the Tibetan population of their ancestors than other East Asian populations, she said. An examination and comparison of the entire genome will be more helpful in pinpointing how and when the advantageous gene was passed on.

The interbreeding may have happened 30,000 to 40,000 years ago, Nielsen said. The variation could have been present in small pockets of the population in lower altitudes, and began to take effect as the people moved higher, he said.

Han Chinese

The same variation was found at a very low rate in genomes of the Han Chinese, the dominant ethnic group in China, compared to the sequenced Tibetan genomes, suggesting the intermixing happened prior to the split between Tibetan and Han Chinese populations.

This instance of modern humans gaining an evolutionary advantage by mating with other species should bring more focus to the importance of adaptive introgression as a mechanism in evolutionary biology, Nielsen said.

“Everything we know about Denisovans we got from one tiny finger bone,” Nielsen said. “There could be hundreds of other species like that out there that contributed advantages to human evolution. We may never know.”