New genetic evidence reveals multiple waves of mixing of modern humans and Neanderthals throughout history

Ever since the discovery of the first Neanderthal bones, scientists have been studying these ancient hominins. How different are they from us? How similar? Did our ancestors interact with them, either amicably or combatively? The recent discovery of the Denisovans, a group similar to the Neanderthals that inhabited Asia and Oceania, has further expanded questions about our past.

Now, an international team of geneticists and artificial intelligence experts brings new findings about the history of genetic interaction among hominins. Led by Joshua Akey, a professor at Princeton's Lewis-Sigler Institute for Integrative Genomics, the researchers have uncovered a history of genetic exchange indicating a much closer connection between these early human groups than previously thought.

"This is the first time geneticists have identified multiple waves of mixing between modern humans and Neanderthals," said Liming Li, a professor in the Department of Medical Genetics and Developmental Biology at Southeast University in Nanjing, China, who conducted this work as a research associate in Akey's lab.

"We now know that modern humans and Neanderthals had contact throughout most of human history," said Akey. Hominins that are our closest ancestors diverged from the Neanderthal lineage about 600,000 years ago, and our modern physical characteristics developed about 250,000 years ago.

"From then until the disappearance of the Neanderthals, which is roughly 200,000 years, modern humans interacted with Neanderthal populations," he added.

The results of their work were published in the current issue of the journal Science.

Neanderthals, who were once stereotypically depicted as slow and limited in abilities, are now seen as skilled hunters and toolmakers who treated their injuries with sophisticated techniques and were well-adapted to the cold European climate.

(Note: all these hominin groups are humans, but to avoid constantly stating "Neanderthal humans," "Denisovan humans," and "ancient versions of our species," archaeologists and anthropologists often use the abbreviations Neanderthals, Denisovans, and modern humans.)

Mapping Gene Flow
Using the genomes of 2,000 living people as well as three Neanderthals and one Denisovan, Akey and his team mapped the gene flow among hominin groups over the last 250,000 years.

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

Akey's team found that even these reference groups, living thousands of miles south of Neanderthal caves, have traces of Neanderthal DNA, likely brought by travelers (or their descendants).

Using the IBDmix tool, Akey's team identified the first wave of contact around 200-250,000 years ago, a second wave 100-120,000 years ago, and the largest wave 50-60,000 years ago.

This is significantly different from previous genetic data. "Previous genetic data suggest that modern humans evolved in Africa about 250,000 years ago, stayed there for the next 200,000 years, and then dispersed out of Africa about 50,000 years ago to settle the rest of the world," said Akey.

"Our models show that there was no long period of stagnation, but that modern humans, shortly after they emerged, began migrating out of Africa and returning to Africa," he said. "To me, this story is about dispersal, that modern humans moved and encountered Neanderthals and Denisovans much more than we previously recognized."

This vision of humanity on the move aligns with archaeological and paleoanthropological research suggesting cultural and tool exchanges among hominin groups.

Genetic Insight
Li and Akey's key insight was to look for modern human DNA in Neanderthal genomes, rather than the other way around. "Most genetic research over the past decade has focused on how mating with Neanderthals affects modern human phenotypes and our evolutionary history — but these questions are relevant and interesting in the reverse case as well," said Akey.

They realized that the descendants of these first waves of mating between Neanderthals and modern humans must have stayed with the Neanderthals, thus leaving traces in their genetic record. "Now that we can include the Neanderthal component in our genetic studies, we see these earlier dispersals in ways we couldn't before," said Akey.

The final piece of the puzzle was the discovery that the Neanderthal population was smaller than previously thought.

Genetic modeling traditionally used variation — diversity — as a proxy for population size. The more diverse the genes, the larger the population. But using IBDmix, Akey's team showed that a significant portion of that apparent diversity comes from DNA sequences taken from modern humans, with their much larger population.

As a result, the effective Neanderthal population has been revised from about 3,400 breeding individuals to about 2,400.

Disappearance of the Neanderthals
When all this is put together, the new findings provide a picture of how the Neanderthals disappeared from the record about 30,000 years ago.

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

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

"Neanderthals were long on the brink of extinction," he said. "If you reduce their numbers by 10 or 20%, which our estimates do, that's a significant reduction for an already endangered population.

"Modern humans were like waves hitting the shore, slowly but steadily eroding that shore. In the end, we demographically overwhelmed the Neanderthals and included them into modern human populations."

Source: Princeton University