This Neandertal girl's toe bone had ancient DNA her ancestors picked up by mating with modern humans more than 100,000 years ago.

This Neandertal girl's toe bone had ancient DNA her ancestors picked up by mating with modern humans more than 100,000 years ago.

Courtesy of Max Planck Institute for Evolutionary Anthropology

Humans mated with Neandertals much earlier and more frequently than thought

Members of our species had sex with Neandertals much earlier—and more often—than previously believed, according to a new study of ancient DNA. As some of the first bands of modern humans moved out of Africa, they met and mated with Neandertals about 100,000 years ago—perhaps in the fertile Nile Valley, along the coastal hills of the Middle East, or in the once-verdant Arabian Peninsula. This pushes back the earliest encounter between the two groups by tens of thousands of years and suggests that our ancestors were shaped in significant ways by swapping genes with other types of humans.

These early modern humans’ own lineages died out, and they are not among the ancestors of living people. But a small bit of their DNA survived in the toe bone of a Neandertal woman who lived more than 50,000 years ago in Denisova Cave in the Altai Mountains of Siberia, Russia. A new analysis of her ancient genome has found that this so-called “Altai” Neandertal inherited DNA from modern humans from Africa, including a gene that may have been involved in speech.

“This is the first genetic evidence that early modern humans met Neandertals and bred with them earlier than we thought,” says lead author Sergi Castellano, an evolutionary biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Ever since researchers sequenced the first full genome of Neandertals in 2010, they have known that the ancestors of European Neandertals interbred with modern humans. By comparing the Neandertal genome with that of modern humans, they found a curious pattern: Present-day Europeans and Asians have inherited about 1% to 3% of their DNA from Neandertals, but Africans have not. This suggested that encounters between modern humans and Neandertals were rare and happened in the Middle East or the Arabian Peninsula after modern humans swept out of Africa, but before they spread widely. When moderns did expand all over Eurasia, they carried that Neandertal DNA in their cells. Later studies of ancient DNA from a 45,000-year-old modern human in Romania helped pinpoint the timing of that encounter to between 50,000 and 65,000 years ago.

More ancient DNA, also from a bone from Siberia’s Denisova Cave, complicated the picture. By sequencing an ancient girl’s finger bone from the cave, researchers discovered a new type of human, the Denisovans, who are closely related to Neandertals but also mated with the ancestors of today’s Melanesians.

With every ancient genome, however, came new surprises. The Denisovan girl’s people had also mated with the ancestors of present-day Melanesians and some mainland Asians (who still carry small amounts of Denisovan DNA) sometime after modern humans encountered Neandertals 50,000 to 65,000 years ago.

So, modern humans had interbred at least twice with archaic humans—Neandertals and, later, Denisovans—after leaving Africa. What’s more, the Denisova girl seemed to also carry some ancient DNA from an even more archaic hominin, such as the direct human ancestor Homo erectus, which lived 1.8 million to roughly 200,000 years ago. Her ancestors had inherited this “super archaic” DNA within the past 400,000 years, but the Altai Neandertal did not have it.

This scenario shows how after human ancestors split with the ancestors of Neandertals, the two groups interbred at least twice—100,000 years ago soon after modern humans emerged and first left Africa, and again between 47,000 and 65,000 years ago.

This scenario shows how after human ancestors split with the ancestors of Neandertals, the two groups interbred at least twice—100,000 years ago, soon after modern humans emerged and first left Africa, and again between 47,000 and 65,000 years ago.

Iian Gronau

How to explain this pattern?

In the new study, published online today in Nature, Castellano and an international team of researchers first zeroed in on the chunks of modern DNA in the genomes of the Altai Neandertal and the Denisovan. By comparing it to key segments of the genomes of 504 Africans, they found that the Altai Neandertal had inherited DNA from modern humans who lived across Africa—and that this “African” DNA was inherited about 100,000 years ago. By contrast, the Denisovan girl and two other Neandertals from Europe (Croatia and Spain) had not inherited that ancient African DNA.

By using modeling to explain the patterns of DNA distribution, the researchers came up with the following scenario: After early modern humans emerged in Africa about 200,000 years ago, some eventually left the continent and mixed with Neandertals in the Middle East or the Arabian Peninsula, where fossils and stone tools of both groups date back to about 120,000 to 125,000 years. This group of modern humans went extinct, but their DNA persisted in the Neandertals that headed east to eventually settle in Siberia. Meanwhile, another group of modern humans left Africa much later and interbred 50,000 to 60,000 years ago with Neandertals that had headed south from Europe to the Middle East. In this later migration, Neandertals interbred with the ancestors of living Europeans and Asians, who then spread throughout Eurasia. Some of this group of modern humans also encountered Denisovans, picking up the DNA that persists today in Melanesians and some Asians.

All of this suggests that modern humans mixed with archaic humans at least three times after they migrated out of Africa. But that’s just a fraction of the intermingling that must have taken place. Neandertals also interbred with Denisovans. And the new study confirms that the Denisovans themselves did indeed interbred with a “superarchaic” hominin, possibly H. erectus, whom they encountered as early as 400,000 years ago. There are also hints that Denisovans interbred with modern humans in Asia more than once, based on different patterns in the distribution of Denisovan DNA in some Chinese and Melanesians. “One would think that mixing has occurred multiple times for a long time,” Castellano says.

The low levels of DNA exchanged by these encounters suggests that it came from only a few trysts—not whole-sale mate-swapping. But it was enough to pass on genes that may have spelled the difference between survival and extinction for modern humans, including Europeans who still have genes from Neandertals that are shaping their health today. The inbred Altai Neandertal also got modern human DNA that may have been involved in speech, the immune system, and the production of sperm, Castellano says. And that fits with the theory that interbreeding was an important and rapid source of genetic diversity that could have been crucial for adapting to new terrain as modern humans spread into foreign lands.

Now, it seems that modern humans picked up Neandertal genes—and passed some of their own DNA back to our close cousins—more than once, almost as soon as our species emerged from Africa, says computational geneticist Sriram Sankararaman of the University of California, Los Angeles, who was not a member of this study. “Admixture between modern humans and Neanderthals predates the out-of-Africa event to which present day non-Africans trace their ancestry.”

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