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Original publication

Martin Kuhlwilm, Ilan Gronau, Melissa J. Hubisz, Cesare de Filippo, Javier Prado, Martin Kircher, Qiaomei Fu, Hernán A. Burbano, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Pavao Rudan, Dejana Brajkovic, Željko Kucan, Ivan Gušic, Tomas Marques-Bonet, Aida M. Andrés, Bence Viola, Svante Pääbo, Matthias Meyer, Adam Siepel and Sergi Castellano
Ancient gene flow from early modern humans into Eastern Neanderthals

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Evolutionary Biology

Early gene flow from modern humans into Neanderthals

Researchers find first genetic evidence of modern human DNA in a Neanderthal individual

February 17, 2016

Using several different methods of DNA analysis, an international research team has identified an interbreeding event between Neanderthals and modern humans that occurred an estimated 100,000 years ago, which is tens of thousands of years earlier than other such events previously documented. They suggest that some modern humans left Africa early and mixed with Neanderthals. These modern humans later became extinct and are therefore not among the ancestors of present-day people outside Africa who left Africa about 65,000 years ago.
Scenario of interbreeding between modern humans and Neanderthals: Neanderthal DNA in present-day humans outside Africa originates from interbreeding that occurred 47,000 – 65,000 years ago (green arrow). Modern human DNA in Neanderthals is likely a consequence of earlier contact between the two groups roughly 100,000 years ago (red arrow). Zoom Image
Scenario of interbreeding between modern humans and Neanderthals: Neanderthal DNA in present-day humans outside Africa originates from interbreeding that occurred 47,000 – 65,000 years ago (green arrow). Modern human DNA in Neanderthals is likely a consequence of earlier contact between the two groups roughly 100,000 years ago (red arrow). [less]

“We knew from Neanderthal DNA found in the genomes of humans outside Africa that Neanderthals and humans have interbred. This interbreeding is estimated to have happened less than 65,000 years ago, around the time that modern human populations spread across Eurasia from Africa. We now find evidence for a modern human contribution to the Neanderthal genome. This is likely the result of much earlier interbreeding”, says Sergi Castellano from the Max Planck Institute for Evolutionary Anthropology, who co-led the study.

Martin Kuhlwilm, co-first author of the new paper, identified the regions of the Altai Neanderthal genome that come from modern humans. “I was looking to see if I could find regions in the genome where the Neanderthal genome from Siberia has sequences resembling those in humans. We know that contemporary non-Africans have traces of Neanderthal in them, so they were not useful to us. So we instead used genomes of contemporary individuals from across Africa to identify mutations which most of them have in common. Some of these mutations occur together in regions of the Altai Neanderthal genome, a sign of interbreeding,” adds Kuhlwilm, who did this work at Max Planck Institute for Evolutionary Anthropology.

In addition to Kuhlwilm and Castellano, the team included several other members of the Max Planck Institute for Evolutionary Anthropology, including Svante Pääbo and Matthias Meyer. The team also included Adam Siepel, who is Chair of CSHL’s Simons Center for Quantitative Biology and co-lead the study, and a former member of Siepel’s Lab, Ilan Gronau, who is now at the Herzliya Interdisciplinary Center, Israel. Melissa Hubisz, a Ph.D. student with Siepel at Cornell University, also made major contributions to the work. The full international research team included 15 additional co-authors.

The team’s evidence of “gene flow” from descendants of modern humans into the Neanderthal genome applies to one specific Neanderthal, whose remains were found in a cave in the Altai Mountains in southern Siberia, near the Russia-Mongolia border. Two Neanderthals from European caves that were sequenced for this study — one from Croatia, another from Spain — both lack DNA derived from modern humans. The team also analyzed the genome of another extinct human, a Denisovan, whose remains were found in the same cave in the Altai Mountains as the Neanderthal bone. Unlike the Neanderthal individual, the Denisovan individual did not carry any modern human DNA. That does not mean modern humans never mated with Denisovans or European Neanderthals. What it does mean, Siepel clarifies, is that “the signal we are seeing in the Altai Neanderthal probably comes from an interbreeding event that occurred after this Neanderthal lineage diverged from its European cousins, a little more than 100,000 years ago.”

Separate paths

The modern human DNA sequences in the Altai Neanderthal appear to derive from a modern human group that separated early from other humans, "about the time present-day African populations diverged from one another, around 200,000 years ago,” adds Gronau, co-first author of this work.

The modern human who contributed genes to this particular Neanderthal individual must have come from a population that left Africa long before the migration of the ancestors of present-day Europeans and Asians from Africa less than 65,000 years ago, the scientists say. Thus, there must have been a long lag between when this group branched off the modern human family tree, roughly 200,000 years ago, and when they left their genetic mark in the Altai Neanderthal, about 100,000 years ago, before themselves being lost to extinction.

PT, SJ/HR

 
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