Life at the top

RESEARCHERS have known for a while that many people alive today carry genes from human species other than Homo sapiens—the result of ancient interbreeding with Neanderthals and Denisovans. They have even worked out that this admixed DNA must often be doing something particularly useful, because its pattern suggests natural selection is actively retaining it. The specifics, though, have not been clear. But in one case they now are, for it is because of these occasional Denisovan ancestors that Tibetans thrive in Tibet.

The plateau of Tibet is one of the most hostile places people inhabit. The air is thin and the weather cold. The locals, nevertheless, do well. And Rasmus Nielsen of the University of California, Berkeley, and his colleagues at BGI, a Chinese DNA-sequencing laboratory, suggest in this week’s Nature that one of the genes which lets them do so is Denisovan.

The Denisovans are a mysterious branch of Homo. They were identified in 2010 by an analysis of the DNA of a bone discovered in a cave (occupied in the 18th century by a hermit called Denis) in the Altai Mountains in Russia. This bone was thought, when found, to be either Neanderthal or modern human, but the analysis showed it was neither. In the wake of that finding, a small percentage of Denisovan DNA has been discovered in various groups of people in Asia and the Pacific islands, Tibetans among them.

The gene Dr Nielsen has been investigating is a version of EPAS-1. This encodes part of a protein called hypoxia-inducible transcription factor 2-alpha. Transcription factors activate other genes, and this one (as its name suggests) does so in response to low oxygen levels. When that happens, it is responsible for stimulating the production of red blood cells, the growth of capillaries and the production of proteins involved in energy generation.

Everybody has some version of EPAS-1, and so everybody can acclimatise to high altitude. But such acclimatisation comes at a price: the extra red cells make blood stickier and more likely to clot, which increases the risk of thrombosis. Except, curiously, in Tibetans. They are well acclimatised without having noticeably raised red-cell counts. And that effect has been tracked down to the particular version of EPAS-1 in their chromosomes.

Dr Nielsen and his team wanted to study the Tibetan version more closely, so they sequenced both it and the area around it in detail. When they did this they discovered that the block of DNA it inhabits is so similar to its Denisovan equivalent that it must originally have come from a mating (maybe more than one) between a Denisovan and Homo sapiens.

Moreover, it is pretty much only Tibetans who have this version of the gene. Dr Nielsen established in 2010 that about 90% of them do, compared with fewer than 10% of their Han Chinese neighbours. He estimated that the altitude-friendly version became this widespread in Tibet in a mere 3,000 years.

His latest study also looked at other groups with Denisovan genes, and could find no trace at all in them of the Denisovan form of EPAS-1. Probably, it is useless or worse at low altitudes, so natural selection has removed it. But, though the Altai Mountains are not as high as Tibet, it might well have been useful there.