Breathless Over New Finding Using Ancient DNA

With one very important exception Tibetans and their Han Chinese neighbors are genetically very similar, but that one difference makes all the difference.tibetanwoman

In the breathlessly thin air of the Himalayas, Tibetans have a genetic variant that makes them keenly well adapted to living on the “roof of the world.” And fascinating new findings by researchers at UC Berkeley indicate that Tibetans can thank an ancient human cousin for that advantage.

There is much about this research that is exciting for us here at 23andMe. (We have a thing about ancient humans.) But the findings are especially thrilling because this is the first time scientists have found a specific trait inherited from ancient humans that is so clearly vital for a modern human population to thrive.

The ancient humans in question are the Denisovans, who scientists only became aware of four years ago after sequencing DNA from bone fragments discovered in a cave in the Altai Mountains in Siberia.

The cave in Siberia where the Denisova bone fragments were found.

The cave in Siberia where the Denisova bone fragments were found.

As modern humans migrated out of Africa about 100,000 years ago, we intermingled with archaic humans such as the Neanderthals and Denisovans, and possibly other not yet identified human cousins. Neanderthals and the Denisovans went extinct about 30,000 years ago but their DNA lives on in modern humans. What role their DNA played in our evolution is difficult to discern.
There are many theories. For instance, Peter Parham, a geneticist at Stanford University School of Medicine, suggested a few years ago that that intermixing gave modern humans a sort of “hybrid vigor.”

It could be that interbreeding with Neanderthals and Denisovans also gave humans an evolutionary shortcut that allowed them to quickly adapt to new environments as they spread across the globe. Indeed in the case of Neanderthals, there is some evidence that their DNA may have contributed to modern humans resistance to certain diseases.

But it cuts both ways and there is evidence suggesting that in some cases Neanderthal DNA, which may have helped from an evolutionary standpoint, may now contribute to risks for certain disease like diabetes and Crohn’s.

“Now that we can estimate the probability that a particular genetic variant arose from Neanderthals, we can begin to understand how that inherited DNA affects us,” said Harvard Medical School geneticist David Reich, earlier this year after publishing a paper on Neanderthal genetic contributions to modern humans in the journal Nature.

The same statement could apply to Denisovans, whose DNA is found in people with ancestry from areas of Oceania, Papua New Guinea and parts of Asia. Now this study has made an important and clear link between Tibetans’ adaption to high altitude and the Denisovans.

Eric Durand, a senior computational biologist at 23andMe, said the study was a rare case of an informed hunch panning out perfectly for the researchers. Eric, who previously developed statistical methods to look at the connection between Neanderthal and Denisovans and modern humans, said the researchers at UC Berkeley discovered a few years ago the variant in the EPAS1 gene that allowed Tibetans to thrive in the oxygen thin air on the Himalayan plain. The question for researchers was how did that variant get there.

Looking at the haplotype structure around EPAS1, as well as the fact that the haplotype is extremely rare in Han Chinese, researchers struggled to explain the genetic adaptation using standard demographic models. They thought that perhaps this special adaptation came from somewhere else, or, maybe more appropriately stated, someone else. So researchers began comparing Tibetan genetic signatures with that of other populations.

Among those was the Denisovan sequence published by Svante Pääbo, an evolutionary geneticist at the Max Planck Institute for Evolutionary Anthropology who first sequenced the Neanderthal genome.

“It’s very satisfying to see that gene flow from Denisovans, an extinct group of archaic humans which we discovered only four years ago, is now found to have had important consequences for people living today,” Svante said recently.

Sometimes looking back can do more than just help scientists understand the past. It can also give them insight into the present.