Princeton study maps 200,000 years of Human–Neanderthal interbreeding

Now, a group of researchers made up of geneticists and artificial intelligence specialists is uncovering new layers of that shared history. Led by Joshua Akey, a professor at Princeton’s Lewis-Sigler Institute for Integrative Genomics, the team has found strong evidence of genetic exchange between early human groups, pointing to a much deeper and more complex relationship than previously understood.

"This is the first time that geneticists have identified multiple waves of modern human-Neanderthal admixture," said Liming Li, a professor in the Department of Medical Genetics and Developmental Biology at Southeast University in Nanjing, China, who performed this work as an associate research scholar in Akey's lab.

"We now know that for the vast majority of human history, we've had a history of contact between modern humans and Neanderthals," said Akey. The hominins who are our most direct ancestors split from the Neanderthal family tree about 600,000 years ago, then evolved our modern physical characteristics about 250,000 years ago.

"From then until the Neanderthals disappeared -- that is, for about 200,000 years -- modern humans have been interacting with Neanderthal populations," he said.

The results of their work were published the journal Science.

Rethinking the Ice Age Stereotype

Neanderthals, once stereotyped as slow-moving and dim-witted, are now seen as skilled hunters and tool makers who treated each other's injuries with sophisticated techniques and were well adapted to thrive in the cold European weather.

(Note: All of these hominin groups are humans, but to avoid saying "Neanderthal humans," "Denisovan humans," and "ancient-versions-of-our-own-kind-of-humans," most archaeologists and anthropologists use the shorthand Neanderthals, Denisovans, and modern humans.)

Using genomes from 2,000 living humans as well as three Neanderthals and one Denisovan, Akey and his team mapped the gene flow between the hominin groups over the past quarter-million years.

The researchers used a genetic tool they designed a few years ago called IBDmix, which uses machine learning techniques to decode the genome. Previous researchers depended on comparing human genomes against a "reference population" of modern humans believed to have little or no Neanderthal or Denisovan DNA.

Akey's team has established that even those referenced groups, who live thousands of miles south of the Neanderthal caves, have trace amounts of Neanderthal DNA, probably carried south by voyagers (or their descendants).

With IBDmix, Akey's team identified a first wave of contact about 200-250,000 years ago, another wave 100-120,000 years ago, and the largest one about 50-60,000 years ago.

Challenging the Out-of-Africa Model

That contrasts sharply with previous genetic data. "To date, most genetic data suggests that modern humans evolved in Africa 250,000 years ago, stayed put for the next 200,000 years, and then decided to disperse out of Africa 50,000 years ago and go on to people the rest of the world," said Akey.

"Our models show that there wasn't a long period of stasis, but that shortly after modern humans arose, we've been migrating out of Africa and coming back to Africa, too," he said. "To me, this story is about dispersal, that modern humans have been moving around and encountering Neanderthals and Denisovans much more than we previously recognized."

That vision of humanity on the move coincides with the archaeological and paleoanthropological research suggesting cultural and tool exchange between the hominin groups.

Li and Akey's key insight was to look for modern-human DNA in the genomes of the Neanderthals, instead of the other way around. "The vast majority of genetic work over the last decade has really focused on how mating with Neanderthals impacted modern human phenotypes and our evolutionary history -- but these questions are relevant and interesting in the reverse case, too," said Akey.

They realized that the offspring of those first waves of Neanderthal-modern matings must have stayed with the Neanderthals, therefore leaving no record in living humans. "Because we can now incorporate the Neanderthal component into our genetic studies, we are seeing these earlier dispersals in ways that we weren't able to before," Akey said.

Shrinking Populations and Genetic Illusions

The final piece of the puzzle was discovering that Neanderthals had a smaller population than researchers previously thought.

Scientists often estimate population size by looking at genetic diversity. In general, more variation in the genome suggests a larger group. But when Akey’s team applied their tool, IBDmix, they found that much of the apparent diversity in Neanderthal DNA actually came from genes inherited from modern humans, who had far larger populations.

With this new insight, scientists lowered their estimate of the Neanderthal breeding population from about 3,400 individuals to roughly 2,400.

Taken together, these findings help explain how Neanderthals disappeared from the fossil and genetic record around 30,000 years ago.
 

"I don't like to say 'extinction,' because I think Neanderthals were largely absorbed," said Akey. His idea is that Neanderthal populations slowly shrank until the last survivors were folded into modern human communities.

This "assimilation model" was first articulated by Fred Smith, an anthropology professor at Illinois State University, in 1989. "Our results provide strong genetic data consistent with Fred's hypothesis, and I think that's really interesting," said Akey.

"Neanderthals were teetering on the edge of extinction, probably for a very long time," he said. "If you reduce their numbers by 10 or 20%, which our estimates do, that's a substantial reduction to an already at-risk population.

"Modern humans were essentially like waves crashing on a beach, slowly but steadily eroding the beach away. Eventually we just demographically overwhelmed Neanderthals and incorporated them into modern human populations."

This research was supported by the National Institutes of Health (grant R01GM110068 to JMA).