Humans and Neanderthals interbred, and scientists now know when

Long ago, early humans shared the earth with several archaic human species, including Neanderthals and Denisovans. These species, were bipedal and close relatives of modern humans. They lived in parts of Northern Africa, Europe, and Asia, while the first populations of modern humans, Homo sapiens, lived in the Horn of Africa. Eventually, as those humans began migrating out of Africa, some came across these archaic human species, and the populations began to interact.

At least since the 1990s, archaeologists have suspected there had been interbreeding between humans and Neanderthals, but genetic evidence emerged when the first draft genome of Neanderthals was published in 2010. Today, we know that an average of 1–3% of the human genome can be traced to Neanderthal ancestry and that the amount varies among people throughout the world. But exactly when that interbreeding occurred remained unclear. Now, thanks in part to ancient DNA sequencing of a 45,000-year-old skull, scientists publishing in Nature and Science have been able to say with certainty that a period of interbreeding between Neanderthals and humans happened roughly 47,000 years ago. This population of interbreeding human was the only group of humans to persist after migrating out of Africa at the time and represents a genetic bottleneck for our species. Therefore, humans who are descended from this interbred population—which the researchers refer to as non-African and includes all people without exclusively central-African ancestry—share Neanderthal gene variants in their DNA from this single interbreeding event (Nature 2024, DOI: 10.1038/s41586-024-08420-x; Science 2024, DOI: 10.1126/science.adq3010).

The two papers share many authors and reach similar conclusions about the timing of this event. But they differ in their methodology and offer their own unique contributions to the discussion surrounding humans’ Neanderthal ancestry.

Research on the Nature paper was led by Johannes Krause, a paleogeneticist at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA), and involved sequencing the genomes from the skull of a human specimen, called Zlatý kůň, that is about 45,000 years old and that was found in the Czech Republic and from similarly aged human bone fragments found in Ranis, Germany. “We have reconstructed genomes from Ranis and Zlatý kůň and they are now the oldest nuclear genomes that we have of modern humans,” Krause says. Those genomes allowed him and his collaborators to peer into the genetic history of humans who lived in Europe at that time.

Arev Sümer, lead author on the Nature paper and a PhD student in Krause’s lab, analyzed the genomic data and compared them with a set of 274 present-day human genomes from people around the world and 57 other ancient human genomes. She says the data show that Zlatý kůň and the Ranis individuals share the same Neanderthal ancestry found in present-day non-African individuals. That means the ancestors of the Ranis individuals, Zlatý kůň, and non-Africans must have come from a single, small group of humans living in Europe between 43,000 and 50,000 years ago that had contact with Neanderthals. “This is important, as it tells us that all modern human remains found outside of Africa that are older than 50,000 years are not from the ancestors of modern-day people,” Sümer says.

Omer Gokcumen, an anthropological genomicist at the University at Buffalo who wasn’t involved in the research, says that not much genomic data from human specimens of this time were available before the Nature paper.“That period is very important, because these guys are [less than 100 generations removed from] the first migrants into Europe, as far as we can tell,” Gokcumen says. “Now we have a really high-quality genome, plus a bunch of pretty good genomes because of this paper.”

Analyses published in the Science paper also confirm that the ancestors of all modern non-African humans came from a single population living in Europe during this time period about 47,000 years ago. That paper doesn’t analyze the newly sequenced genomic data from Ranis or Zlatý kůn; instead, it uses previously sequenced modern and ancient human genomes to evaluate how the parts of human DNA that contained Neanderthal ancestry evolved over time. In addition to confirming the time period of interbreeding, the paper shows that “the majority of selection, positive and negative, on Neanderthal ancestry happened very quickly after the gene flow, within roughly 100 generations,” says Leonardo Iasi a geneticist at MPI-EVA and lead author on the paper.

Iasi explains that some Neanderthal gene variants, including variants of genes related to the immune system and skin pigmentation, were beneficial and increased in frequency throughout the human population. Other variants were deleterious, and natural selection removed those genes from humans. Notably, the human X chromosome is devoid of Neanderthal gene variants and seemingly underwent very rapid selection against those Neanderthal variants.

Gokcumen says the Science paper is “very strong methodologically” and adds a unique temporal aspect to our understanding of how natural selection acted on the gene variants that Neanderthals contributed to humans. But many questions remain that these papers don’t address. It’s still unclear how subsequent human interbreeding with archaic human species may have contributed to variation in the amount of Neanderthal gene content across populations and why some Neanderthal gene variants are beneficial while others are not.