Up to 4 percent of the DNA of people today who live outside Africa came from Neandertals, the result of interbreeding between Neandertals and early modern humans. That conclusion comes from scientists led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, who pieced together the first draft of the Neandertal genome—which represents about 60 percent of the entire genome—using DNA obtained from three Neandertal bones that come from Vindija Cave in Croatia and are more than 38,000 years old.
The evidence that Neandertals contributed DNA to modern humans came as a shock to the investigators, who published their findings in the May 7, 2010, Science issue. “First I thought it was some kind of statistical fluke,” Pääbo remarked during a press teleconference. The finding contrasts sharply with his previous work. In 1997 he and his colleagues sequenced the first Neandertal mitochondrial DNA. Mitochondria are the cell's energy-generating organelles, and they have their own DNA, which is distinct from the much longer DNA sequence that resides in the cell's nucleus. Their analysis revealed that Neandertals had not made any contributions to modern mitochondrial DNA. Yet because mitochondrial DNA represents only a tiny fraction of an individual's genetic makeup, the possibility remained that Neandertal nuclear DNA might tell a different story. Still, additional genetic analyses have typically led researchers to conclude that Homo sapiens arose in Africa and replaced the archaic humans it encountered as it spread out from its birthplace without mingling with them—the out of Africa replacement scenario, as it is known.
But mingle they apparently did. When Pääbo's team looked at patterns of nuclear genome variation in present-day humans, it identified 12 genome regions where non-Africans exhibited variants that were not seen in Africans and that were thus candidates for being derived from the Neandertals, who lived not in Africa but Eurasia. Comparing those regions with the same regions in the Neandertal sequence, the researchers found that 10 of these 12 variants in non-Africans came from Neandertals. The contributions did not seem to encode anything of functional importance, although subsequent analysis has hinted that Neandertals may have passed along disease-fighting genes.
Intriguingly, the researchers failed to detect a special affinity to Europeans—a link that might have been expected given that Neandertals seem to have persisted in Europe longer than anywhere else before disappearing around 28,000 years ago. Rather the Neandertal sequence was equally close to sequences from present-day people from France, Papua New Guinea and China. By way of explanation, the investigators suggest that the interbreeding occurred in the Middle East between 50,000 and 80,000 years ago, before moderns fanned out to other parts of the Old World and split into different groups.
Intermixing does not surprise paleoanthropologists who have long argued on the basis of fossils that archaic humans, such as the Neandertals in Eurasia and Homo erectus in East Asia, mated with early moderns and can be counted among our ancestors—the so-called multiregional evolution theory of modern human origins. The detection of Neandertal DNA in present-day people thus comes as welcome news to these scientists. “It is important evidence for multiregional evolution,” comments Milford H. Wolpoff of the University of Michigan, the leading proponent of the theory.
In a prepared statement, out of Africa theorist Christopher B. Stringer of the Natural History Museum in London acknowledged that the genome results show that “many of us outside of Africa have some [Neandertal] inheritance.” But Stringer maintains that the origin of our species is mostly an out of Africa story. Population geneticist Laurent Excoffier of the University of Bern in Switzerland agrees, noting that the alleged admixture did not continue as moderns moved into Europe. “In all scenarios of speciation, there is a time during which two diverging species remain interfertile,” he explains.
In addition to illuminating how early humans interacted, the Neandertal genome is helping to indicate which parts of the modern human genome separate us from all other creatures. Thus far Pääbo's group has identified a number of modern human genome regions containing sequence variation that is not seen in Neandertals and that may have helped modern humans adapt. Some of these regions are involved in cognitive development, sperm movement and the physiology of the skin.
Exactly how these slight changes to the modern human sequence affected the functioning of these genome regions remains to be determined. Says Pääbo: “This is just the beginning of the exploration of human uniqueness that is now possible.”