Climbing a mountain in Tibet is no easy feat. The atmosphere is already thin on the world’s highest plateau—the oxygen level is just 60 percent of what it is at sea level—and adding elevation makes breathing even more strained. As a teenager, I once went on a hike in Kunming, a neighboring Chinese province with not quite Lhasa-levels of altitude. Even with a supplemental bagful of air (helpfully provided by tour guides), I couldn’t make it up a diminutive hill. Yet pious Tibetan Buddhists at Darchen, at the base of the Mount Kailash, complete pilgrimages to the mountain starting at 4,575 meters of elevation (15,010 feet), continuing upward while prostrating themselves at each step.
Tibetans live in a region that averages more than 4,000 meters above sea level. (Not for nothing is it called the roof of the world.) How did they come to be able to cope with their extreme environs? Some researchers in China and the United States think they might know, and their findings were published Wednesday in Nature. By sequencing DNA from a group of Tibetans and comparing the code to other gene databases, the researchers have discovered that Tibetans are inheritors of an ancient trait that helps regulate the oxygenation in their blood. But surprisingly, this trait did not arise in Homo sapiens. Rather, it came from another group of humans, the Denisovans—mysterious, little-known hominid cousins that died out some 40,000 years ago.
Homo sapiens are the only modern human species, but there were others not too long ago. Interbreeding with these groups means some of their genes remain in us today: Recent research has shown that most Europeans and Asians are about 1 to 3 percent Neanderthal, for example. The existence of Denisovans only became known in 2010 when DNA from two teeth and a pinkie bone found in a Siberian cave was sequenced. It was the first new human species identified solely through genetic means (rather than through physical remains). Homo sapiens and Neanderthals once occupied the cave, too, and scientists suspected that perhaps Denisovans and modern humans might have intermingled and bred. Subsequent research confirmed this: Melanesians’ and Australian aborigines’ genes are 3 to 5 percent Denisovan, and throughout Asia, genetic evidence of the lineage remains, though to smaller degrees.
The new study on Tibetans demonstrates for the first time an evolutionary advantage conferred directly by Denisovans, an adaptation that seems to be singular to the Tibetan people. For people whose ancestors lived in milder altitudes, experiencing a dearth of oxygen at great heights causes the level of hemoglobin, the protein that carries oxygen in blood, to increase in attempt to compensate. But this raises the likelihood of cardiac events in the short term, and it is unhelpful for reproduction, as it increases the risk of preeclampsia (hypertension during pregnancy). Tibetans don’t have the same reaction to elevation: They have greater fitness and higher fertility even when there is little to breathe. This, along with other respiratory adaptations, allows them to thrive where others cannot.
The genetic basis for the Denisovan-inherited adaptation in Tibetans involves a protein called EPAS1 that controls oxygen regulation. (Andeans also have a beneficial oxygen regulatory mechanism, but through a different protein, evolved from a different lineage.) The new analysis shows that the particular sequence of genes encoding for how EPAS1 functions in Tibetans was not a random, auspicious mutation. In fact, the same genetic pattern is found in Denisovan DNA.
Denisovans and Neanderthals are called extinct human “species”—a term that used to demark a clear line between two organisms incapable of interbreeding to produce fertile offspring. But the definition is no longer so clear. We know that these hominin cousins did couple with our Homo sapien ancestors—and some of us have inherited from them valuable modern traits. How we define “humans” past and present is a subject to contemplate—as fitting for scientists as for pilgrims to think about on their journeys across Tibetan plains.
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