Some of the last Denisovans may have intermingled with modern humans in mountainous New Guinea or on nearby islands.

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Our mysterious cousins—the Denisovans—may have mated with modern humans as recently as 15,000 years ago

CLEVELAND, OHIO—The elusive Denisovans, the extinct cousins of Neanderthals, are known from only the scraps of bone they left in Siberia’s Denisova Cave in Russia and the genetic legacy they bequeathed to living people across Asia. A new study of that legacy in people from New Guinea now suggests that, far from being a single group, these mysterious humans were so diverse that their populations were as distantly related to each other as they were to Neanderthals.

In another startling suggestion, the study implies one of those groups may have survived and encountered modern humans as recently as 15,000 to 30,000 years ago, tens of thousands of years later than researchers had thought. “A late surviving lineage [of Denisovans] could have interbred with Homo sapiens” in Southeast Asia, paleoanthropologist Chris Stringer of the Natural History Museum in London, not a member of the team, said in a Skype interview during a session at the annual meeting of the American Association of Physical Anthropologists here. The new study was presented Thursday at the meeting.

Researchers already knew that living people from a vast area spanning the Philippines and New Guinea to China and Tibet have inherited 3% to 5% of their DNA from Denisovans. The leading scenario had suggested that as modern humans swept out of Africa, they first encountered Neanderthals and mated with them; hence, all people in Europe and Asia now have 1% to 3% of their DNA from Neanderthals. The ancestors of Asians then encountered Denisovans 50,000 years ago or so and acquired 3% to 5% of their DNA from them.

For the new study, an international team analyzed the complete genomes of 161 people from 14 groups in Indonesia and Papua New Guinea. In the DNA of 60 people from New Guinea, population biologist Murray Cox of Massey University in Palmerston North, New Zealand, and molecular biologist Herawati Sudoyo of the Eijkman Institute for Molecular Biology in Jakarta, and their colleagues found an unexpected twist. The first Denisovan DNA discovered, from the Siberian cave, comes from a single population (which geneticists have labeled D0). But “Papuans carry DNA from at least two [other] Denisovan populations, called D1 and D2,” Cox said in his talk, which was filmed in advance and played at the meeting.

When the team members analyzed the DNA with three statistical methods, they found that the two additional sources of Denisovan DNA came from populations so distantly related that they had diverged more than 283,000 years ago. And the D2 population is most distant from the Siberian Denisovans, splitting off roughly 363,000 years ago. That makes those two populations almost as distantly related to each other as they are to Neanderthals, Cox says. “We used to think of Denisovans as a single group,” notes Cox, who suggests as an aside that the D2 group might even need a new name.

The D1 DNA isn’t found in people outside New Guinea, and it’s found on large chunks of chromosome that haven’t been mixed over time, suggesting it entered the modern human genome from 15,000 to 30,000 years ago. Cox’s team suggests a late group of Denisovans survived in the remote mountains of New Guinea or islands of Indonesia and mated with modern humans.

The finding of two Denisovan lineages in Southeast Asia adds to results reported in Cell last year by Sharon Browning of the University of Washington in Seattle and her colleagues. They had suggested that New Guineans had a separate source of Denisovan DNA than people in East Asia, suggesting at least two mixing events.

The multiple encounters with Denisovans gave living people in Indonesia and New Guinea 400 new gene variants, including an immune gene variant (TNFAIP3) and a gene involved in diet (WDFY2). “People are turning up in hospitals in Australia carrying this gene [TNFAIP3]; it has clinical implications for how they respond to autoimmune diseases,” Cox said in his talk.

Not everyone is convinced by the late dates Cox proposes. “There are definitely multiple Denisovan populations, but the claim that they interbred 15,000 to 30,000 years ago is extraordinary,” population geneticist Benjamin Vernot of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, told Science.

“I’m skeptical,” added Cosimo Posth of the Max Planck Institute for the Science of Human History in Jena, Germany. He suggests the hints of a late mating could reflect an encounter of previously isolated modern populations rather than of moderns and Denisovans. In this scenario, modern humans mated with Denisovans, then the modern populations diverged, with each branch retaining a different set of Denisovan genes. The moderns then reconnected, mixing the two sets of Denisovan DNA together again.

Whatever happened on New Guinea, it seems Denisovans were a far-flung diverse group that mixed with modern humans frequently. In a separate talk, Xinjun Zhang of the University of California, Los Angeles, reported that Tibetans also got their Denisovan DNA from two different encounters.