Ancient DNA Reveals Neandertal Gene Flow into Modern Humans

Ancient DNA research suggests that our non-African ancestors mixed with Neandertals about 50,000 years ago, resulting in one to two percent Neandertal DNA in non-African modern humans. In a study of 300 genomes, researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig and the University of California, Berkeley found that this likely occurred in a single instance about 47,000 years ago, suggesting a human migration out of Africa no later than 43,500 years ago. Some Neandertal variants likely helped humans adapt outside of Africa, while others, now absent among modern humans, were possibly removed soon after the admixture event.

The study of ancient DNA has greatly advanced our knowledge of human evolution, including the discovery of gene flow from Neandertals into the common ancestors of modern humans. Neandertals and modern humans diverged about 500,000 years ago, with Neandertals living in Eurasia for the past 300,000 years. Then, sometime around 40,000 to 60,000 years ago, modern human groups left Africa and spread across Eurasia, encountering Neandertals along the way. As a result, most non-Africans harbor one to two percent Neandertal ancestry today. However, the precise timing and functional legacy of Neandertals remains elusive.

In a new study, researchers from the Max Planck Institute for Evolutionary Anthropology, Leipzig, and the University of California, Berkeley, examined the genomes of 300 present-day and ancient modern humans, including 59 individuals who lived between 2,000 and 45,000 years ago. "We set out to determine the timing and duration of Neandertal gene flow and the resulting impact on modern humans. To do this, we created a catalog of Neandertal ancestry segments. By comparing the segments among individuals from different time periods and geographic locations, we were able to show that the vast majority of Neandertal ancestry can be traced to a single, shared, extended period of gene flow into the common ancestors of all non-African individuals today," says Priya Moorjani from the University of California, Berkeley.

Neandertal Ancestry Revisited

By observing the length of the Neandertal DNA segments, which is related to the number of generations since the gene flow, the researchers inferred that the gene flow began about 50,000 years ago and continued for about 7,000 years. "This timeline closely matches the archaeological evidence for the overlap of Neandertals and modern humans in Europe. Some early modern humans - Oase, Ust'-Ishim, Zlatý kůň, and Bacho Kiro - possess substantial unique Neandertal ancestry that is not shared with modern humans after 40,000 years," says first author Leonardo Iasi from the Max Planck Institute for Evolutionary Anthropology.

These dates have several implications for human dispersal after the Out-of-Africa event, as they provide a lower bound on the timing of migration and the settlement of regions outside of Africa. For example, this suggests that the major migration out of Africa occurred no later than 43,500 years ago. Moreover, the population receiving Neandertal ancestry may have been highly structured during the gene flow event. "Diversification of humans outside of Africa may have begun during or soon after the Neandertal gene flow, which could partially explain the different levels of Neandertal ancestry among non-African populations and also reconcile our dates with archaeological evidence for the presence of modern humans in Southeast Asia and Oceania by about 47,000 years," says Benjamin Peter from the Max Planck Institute for Evolutionary Anthropology and the University of Rochester. "Studying more ancient genomes from Eurasia and Oceania could further our understanding of when humans spread to these regions."

Functional Impact of Neandertal Ancestry

To understand the functional legacy of Neandertal ancestry, the researchers examined changes in Neandertal ancestry across the genome and over time. They identified some Neandertal regions that are present at high frequency, possibly because they were beneficial as early modern humans began to explore new environments outside of Africa.

These include genes related to immune function, skin pigmentation and metabolism. On the other hand, there are also large regions of the genome that are completely devoid of Neandertal ancestry. These regions formed rapidly after the gene flow and were also absent from the earliest modern human genomes, 30,000 to 45,000-year-old individuals. Many Neandertal sequences may have been deleterious to humans and were therefore actively and rapidly selected against by evolution."

Manjusha Chintalapati, University of California, Berkeley

This study sheds light on the complex history of gene flow from Neandertals into modern humans. It also highlights the power of genomic data to elucidate the legacy of human migrations and gene flow.