The New York Times, February 17, 2016

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In 1997, scientists found the first scrap of Neanderthal DNA in a fossil. Since then, they have recovered genetic material, even entire genomes, from a number of Neanderthal bones, and their investigations have yielded a remarkable surprise: Today, 1 to 2 percent of the DNA in non-African people comes from Neanderthals.

That genetic legacy is the result of interbreeding roughly 50,000 years ago between Neanderthals and the common ancestors of Europeans and Asians. Recent studies suggest that Neanderthal genes even influence human health today, contributing to conditions from allergies to depression.

Now scientists have found that the genes flowed both ways. In a study published on Wednesday in Nature, a team of scientists reports that another instance of interbreeding left Neanderthals in Siberia with chunks of human DNA.

This exchange, the scientists conclude, took place about 100,000 years ago. That’s a puzzling date, because a great deal of evidence indicates that the ancestors of today’s non-Africans did not expand out of Africa until 50,000 to 60,000 years ago.

It’s possible, then, that these Neanderthals acquired DNA from a mysterious early migration of humans.

“I think at this point we’ve convinced everybody the observation is real,” said Adam Siepel, a geneticist at Cold Spring Harbor Laboratory and a co-author of the new study. “But the story behind the observation is still very much in dispute.”

Humans and Neanderthals split from a common ancestor in Africa about 600,000 years ago. At some point afterward, the ancestors of Neanderthals spread to Europe, the Middle East and Central Asia.

Along the way, Neanderthals took on a distinctive anatomy — a stocky, powerful build — and became impressive hunters of big game. The last Neanderthals appear to have died about 40,000 years ago.

In 2010, scientists at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, recovered about 60 percent of a Neanderthal genome from fossils found in a Croatian cave. Neanderthals shared certain mutations with living Europeans and Asians, the scientists found — but not with modern Africans. They concluded that humans must have interbred with Neanderthals after leaving Africa.

Three years later, the Max Planck team reconstructed the complete genome of a male Neanderthal from a toe bone dating back at least 50,000 years, which had been discovered in the Altai Mountains of Siberia. Comparing the Altai genome to modern human DNA confirmed the interbreeding.

Recently, the researchers harvested more DNA from European Neanderthal fossils, putting together very detailed reconstructions of a single chromosome, Chromosome 21.

Sergi Castellano, a geneticist at Max Planck Institute, set out to compare this European Neanderthal DNA to the genes from Siberia. He was curious about how isolated the populations of Neanderthals were from one another, and how they were related to humans alive today.

He was joined by Dr. Siepel, who has developed powerful statistical models in recent years to trace how DNA changes over time. He and his colleagues are able to compare genomes and infer their common history: how their ancestors split apart, for example, and how large the populations of their ancestors were.

Dr. Siepel, Dr. Castellano and their colleagues used these models to analyze the Neanderthal DNA and that of humans. Their analysis confirmed previous studies: Some Neanderthal DNA did indeed end up in modern Europeans and Asians.

But they also found another example of so-called gene flow, and an unexpected one at that: The Altai Neanderthals in particular shared some mutations with living Africans, but not with Europeans and Asians.

That pattern suggests that an African lineage of humans interbred with the ancestors of the Altai Neanderthals after they split from other Neanderthals.

Dr. Castellano and Dr. Siepel thought at first there was something wrong with their analysis, so they went back to fix it. But when they looked for the problem, they could not find it.

“We poked and prodded and poked and prodded, and couldn’t get it to go away,” said Dr. Siepel.

Once the scientists accepted that the interbreeding was real, they estimated when it happened. When DNA gets passed down through the generations, it gets shuffled into new arrangements that can be used to build a sort of timeline.

Based on this gene shuffling, the scientists estimated that humans and the ancestors of the Altai Neanderthals interbred about 100,000 years ago — long before people were thought to have left Africa. “This observation throws a wrench in the works,” said Dr. Siepel.

Bence Viola, a paleontologist at the University of Toronto and a co-author of the new study, said he was skeptical when he first learned of the genetic data. “It’s really weird, that’s my main impression,” he said.

Eventually, however, Dr. Castellano persuaded him the data were strong, and Dr. Viola looked over the fossil record for possible explanations for the interbreeding.

In the 1930s, for example, scientists discovered 120,000-year-old fossils in Israel that looked a lot like living humans. Many scientists viewed them as a failed human migration from Africa, with no genetic connection to humanity today.

In October, Chinese researchers discovered another intriguing clue in a cave: 47 teeth that they estimate are between 80,000 and 120,000 years old. The scientists argue that the teeth belonged to modern humans.

Dr. Viola is not completely convinced by the Chinese study. Instead, he thinks the scenario that best fits the evidence is that humans expanding into the Middle East encountered and interbred with Neanderthals there. The Neanderthals then migrated east to Siberia, taking human DNA with them.

“It seems pretty solid,” said Jonathan K. Pritchard, a geneticist at Stanford University who was not involved in the study. “Overall, the story they’re telling is pretty coherent.”

Dr. Pritchard said that more examinations of ancient DNA would help resolve the many questions raised by the new study and help scientists understand the scope of the intimate back-and-forth between Neanderthals and humans.

“There’s going to be a lot more data really soon,” he said. “I would expect in the next few years we’ll have much, much more of the jigsaw puzzle, and it will be possible to piece this all together.”

Copyright 2016 The New York Times Company. Reprinted with permission.