Study shows Neanderthals inherited at least 6% of their genome from a now-extinct lineage of early modern humans

Seventy-five thousand years ago, modern humans traveled to Eurasia, where they met and interbred with Neanderthals. It turns out that Neanderthals were already carrying human DNA from a far earlier interaction with modern humans, according to a recent study published in the journal Current Biology.

The research team led by Penn, with participation from the Universities of Addis Ababa, Botswana, Fudan, Hubert Kairuki Memorial, and Yaoundé, demonstrated that an extinct lineage of modern humans migrated to Eurasia more than 250,000 years ago, where they interbred with Neanderthals. These people eventually went extinct, leaving a population that was primarily descended from Neanderthals.

Alexander Platt is a senior research scientist at the Perelman School of Medicine and one of the study's initial authors. "We found this reflection of ancient interbreeding where genes flowed from ancient modern humans into Neanderthals," he adds. "These people departed from Africa somewhere between 250,000 and 270,000 years ago. They were far more like us than Neanderthals, and they were related to all modern humans."

By contrasting a variety of genomes from contemporary indigenous groups in sub-Saharan Africa with a Neanderthal genome, the researchers were able to draw this result.

Senior author of the study and a professor at Penn Integrates Knowledge University, Sarah Tishkoff, states, "This study highlights the importance of including ethnically and geographically diverse populations in human genetics and genomic studies."

Neanderthal ancestry is expected to be limited in sub-Saharan Africa because the majority of Neanderthal-human interbreeding is thought to have occurred in Eurasia rather than Africa. However, a recent study made the startling discovery that several sub-Saharan populations contain segments of DNA that resemble Neanderthal DNA. The study could not find out how this Neanderthal-like DNA got into these populations, if it came from modern humans who had once migrated from Africa, interbred with Neanderthals in Eurasia, and then moved back to Africa, or if it came from a previous human-Neanderthal encounter.

It was also unclear if Neanderthal-like DNA is common among sub-Saharan people because the study relied on a small number of genomes from the 1,000 Genomes Project, all of which share a relatively recent common ancestor in Central and Western Africa.

Tishkoff's team used a genetically varied sample of 180 individual genomes from 12 distinct communities in Cameroon, Botswana, Tanzania, and Ethiopia to better understand how ubiquitous these Neanderthal-like DNA regions are across sub-Saharan Africa and to unravel their origins. The scientists located Neanderthal-like DNA areas and searched for Neanderthal ancestry in each genome.

Next, they made a comparison between the genomes of current humans and a Neanderthal that lived about 120,000 years ago. The researchers used a cutting-edge statistical technique to compare the two groups and ascertain where the Neanderthal-like DNA originated in these contemporary sub-Saharan populations—from modern humans who inherited the region from Neanderthals, or from modern humans who inherited it from Neanderthals and brought it back to Africa.

They discovered that Neanderthal-like DNA was present in every sub-Saharan community, suggesting that this phenomena is common. Most of the time, the old lineage of modern humans that gave rise to Neanderthals when they moved from Africa to Eurasia around 250,000 years ago is the source of this Neanderthal-like DNA. Approximately 6% of the Neanderthal genome was inherited from modern humans as a result of this interbreeding between modern people and Neanderthals.

The researchers also discovered evidence of Neanderthal heritage in some sub-Saharan communities, which was brought to these populations when people with Neanderthal DNA came back into Africa. The Amhara from Ethiopia and the Fulani from Cameroon had the greatest percentages of Neanderthal ancestry among these sub-Saharan groups, which varied from 0 to 1.5%.

The researchers also looked at the locations of these pieces of contemporary human DNA to try to determine if carrying it was beneficial or detrimental when inserted into the Neanderthal genome. The researchers also looked at the locations of these contemporary human DNA segments inside the Neanderthal genome in an effort to determine if harboring modern human DNA was advantageous or detrimental. The majority of the modern human DNA was discovered to be in noncoding regions of the Neanderthal genome, suggesting that the presence of modern human genes in a Neanderthal background is detrimental to fitness. This finding also suggests that modern human gene variants were being preferentially lost from coding sections of the genome.

This is comparable to what has been observed in contemporary humans, when Neanderthal genes have been gradually eliminated from populations due to natural selection. "A Neanderthal allele may therefore function perfectly in Neanderthals, but when it is inserted into the current human genome, it causes issues. Neanderthals and modern humans both gradually eliminated the other group's alleles," according to Platt.

"In the almost 500,000 years between the ancestors of Neanderthals splitting off from the ancestors of modern humans and these other modern humans being reintroduced to Neanderthal populations, we had become such different organisms that, although we were still able to interbreed quite readily, the hybrids didn't work so well, which means we were very far along the path to becoming distinct species."

By locating a genetic reference of a population that is on a branch of the human family tree that was previously absent from the genomic and fossil record, this research provides new opportunities for studying the evolution of humans.

The second first author of the paper, Daniel Harris, is a postdoctoral research researcher at the Perelman School of Medicine. "Discovering this ancient lineage of modern humans is really exciting for future research because it gives us a different lens to look at human evolution," Harris says. "Because we don't have DNA sequences from modern human fossils from that long ago, identifying these sequences will shed light on very early modern human evolution in Africa."