Neanderthal DNA accounts for about 1-2% of the genomes of individuals who are not of African descent. In a recent study, scientists examined the lengths of Neanderthal DNA segments in 58 ancient Eurasian genomes of early modern humans, determining that these genes were introduced through interbreeding between Homo sapiens and Neanderthals roughly 47,000 years ago during a significant period spanning around 7,000 years. Their research provides vital insights into the timeline of human migration out of Africa and the subsequent spread of Homo sapiens.
An in-depth analysis of ancient modern human DNA (Homo sapiens) from Europe and Asia has pinpointed the timeframe when interbreeding with Neanderthals occurred, starting around 50,500 years ago and lasting roughly 7,000 years—until the decline of Neanderthals.
This interbreeding led to Eurasians inheriting numerous genes from our Neanderthal relatives, which currently constitute between 1% and 2% of our genomes.
The genome-based estimates align well with archaeological findings indicating that modern humans and Neanderthals coexisted in Eurasia for approximately 6,000 to 7,000 years. This analysis, utilizing both contemporary human genomes and the ancient genomes excavated from modern human bones across Eurasia, established an average date for the Neanderthal-Homo sapiens interbreeding at around 47,000 years ago. Previous estimates for the timing of this interbreeding ranged from 54,000 to 41,000 years ago.
Additionally, these new dates suggest that the early migration of modern humans from Africa into Eurasia was largely completed by about 43,500 years ago.
“The timing is crucial as it greatly informs our understanding of the out-of-Africa migration, given that a majority of non-Africans today possess 1-2% Neanderthal ancestry,” stated Priya Moorjani, an assistant professor of molecular and cell biology at UC Berkeley and one of the lead authors of the study. “This timing also sheds light on the settlement patterns of regions outside Africa, which are generally analyzed through archaeological findings or fossils discovered in diverse global locations.”
The research, conducted under the direction of Benjamin Peter from the University of Rochester and the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig, Germany, is set to be published in the December 13 issue of Science. The principal authors for this work include Leonardo Iasi, a graduate student at MPI-EVA, and Manjusha Chintalapati, a former postdoc at UC Berkeley, now at Ancestry DNA.
The extended period of interbreeding may explain the observation that East Asians have around 20% more Neanderthal genes compared to Europeans and West Asians. If modern humans migrated east around 47,000 years ago, as suggested by various archaeological sites, they would have already carried intermingled Neanderthal genes.
“Our findings reveal that the interbreeding period was complex and likely extended over a long time. Distinct groups might have separated during the 6,000 to 7,000-year timeframe, with some continuing to mix for a longer duration,” Peter remarked. “However, a unified timeframe for gene flow aligns best with our data.”
“One of the primary outcomes of this study is the accurate dating of the Neanderthal admixture, a process that was previously estimated using isolated ancient samples or contemporary individuals. No one had attempted to model the data from all ancient samples collectively,” Chintalapati explained. “This approach enabled us to create a more comprehensive view of history.”
Neanderthal deserts in the genome
In 2016, Moorjani developed a method to deduce the timing of Neanderthal gene flow using often incomplete ancient genomes. At that time, only five archaic Homo sapiens genomes were accessible. For the current study, Iasi, Chintalapati, and their colleagues applied this methodology to analyze 58 previously sequenced genomes of ancient Homo sapiens sourced from Europe, Western, and Central Asia over the last 45,000 years, alongside genomes from 275 modern humans worldwide, arriving at an exact date of 47,000 years ago. Instead of presuming that gene flow occurred within a single generation, they utilized more intricate models developed by Iasi and Peter, indicating that the interbreeding transpired over an extended 7,000 years rather than sporadically.
The interbreeding timeline between Neanderthals and modern humans was further supported by an independent study from MPI-EVA researchers, which is scheduled for publication on December 12 in the journal Nature. This examination of two newly sequenced ancient Homo sapiens genomes, dating back approximately 45,000 years, also corroborated the 47,000-year timeframe.
“Though these ancient genomes were previously published, they had not been analyzed in relation to Neanderthal ancestry in such detail. We established a catalog of Neanderthal ancestry segments in modern humans. By analyzing all these samples together, we concluded that the gene flow happened over roughly 7,000 years,” Chintalapati added. “The Max Planck group sequenced new ancient DNA samples, allowing them to more directly date the Neanderthal gene flow, which yielded similar results to ours.”
The UC Berkeley/MPI-EVA team also scrutinized the regions of the modern human genome that include inherited Neanderthal genes and those entirely without Neanderthal DNA, termed Neanderthal deserts. They observed that these barren areas formed rapidly following the interbreeding, which suggests that certain Neanderthal gene variants located in those genomic regions may have been harmful to modern humans.
Ancient modern human remains older than 40,000 years—such as those from Oase cave in Romania, Ust’-Ishim in Russia, Zlatý k?? in the Czech Republic, Tianyuan in China, and Bacho Kiro in Bulgaria—exhibited these genomic deserts.
“Our findings indicate that very early modern humans from 40,000 years ago possess no ancestry in these deserts, implying that these remarkable regions formed shortly after gene flow,” Iasi noted. “We also tracked the changes in Neanderthal ancestry frequency over time and across the genome, identifying regions that are present at high frequencies, likely due to beneficial variants that were integrated from Neanderthals.”
The majority of high-frequency Neanderthal genes are associated with immune function, skin pigmentation, and metabolism, as highlighted in previous research. For instance, one immune gene variant inherited from Neanderthals provides protective effects against the coronavirus causing COVID-19. Certain Neanderthal genes related to immunity and skin color have actually increased in frequency in Homo sapiens over time, suggesting they may have provided evolutionary advantages.
“Neanderthals inhabited harsh, Ice Age climates outside Africa, adapting to both the environment and the pathogens present there. When modern humans migrated out of Africa and mixed with Neanderthals, some individuals inherited Neanderthal genes that presumably enhanced their ability to survive and thrive,” stated Iasi.
“The fact that we detect some of these beneficial regions in samples dated 30,000 years ago indicates that they were likely advantageous right after the gene flow,” Chintalapati remarked.
Other genes, such as one that offers resistance to coronaviruses, may not have been immediately advantageous but gained importance later on.
“Environments change, leading some genes to become beneficial,” Peter commented.
Moorjani is currently examining Neanderthal sequences in individuals of East Asian heritage, who not only have a higher percentage of Neanderthal genes but also some genes—accounting for up to 0.1% of their genomes—from another early hominin group known as Denisovans.
“It’s fascinating that we can delve into the past and observe how genetic variants inherited from our evolutionary relatives, Neanderthals and Denisovans, have evolved over time,” Moorjani concluded. “This work enhances our understanding of the interactions between Neanderthals and modern humans.”
Additional co-authors of the Science paper include postdoctoral fellow Laurits Skov from UC Berkeley, and Alba Bossoms Mesa and Mateja Hajdinjak from MPI-EVA. Moorjani’s research received support from the Burroughs Wellcome Fund and the National Institutes of Health (R35GM142978).
