Neanderthal Genome Rewrites Human Evolution

Last year, an international team of researchers announced that they had completed the first draft of the Neanderthal genome–more than three billion nucleotides, sequenced from three minute samples of bone powder. Now, in two papers published today in Science, the group reveals in-depth analyses of the data and provides an unparalleled glimpse at human evolution. By comparing Neanderthal DNA with that of living humans from around the world, the scientists have found evidence that–sometime between 50,000 and 80,000 years ago–modern humans and Neanderthals interbred.

Archeologists’ traditional view of human evolution, gleaned from carbon dating, skeletal structure, fossil location, and, more recently, Neanderthal mitochondrial DNA, posits that humans today are descended from a small group of individuals that migrated out of Africa and dispersed throughout the world. But the new research shows that modern humans in Africa have a lower percentage of the Neanderthal genome than non-Africans do–implying that the founder group that left Africa interbred with Neanderthals before moving on to populate the other continents. “Likely, it took place somewhere in the Middle East or in northern Africa, perhaps at the gateway as they were migrating out for the first time,” says Harvard University geneticist David Reich, who performed the population genetics analyses.

The scientists used just half a gram of bone powder, collected from the bones of three individual Neanderthals excavated from the Vindija Cave in Croatia. The data they provide tells a story not just of migration but physical evolution, and allows researchers to isolate what makes humans unique. “The Neanderthals are our closest evolutionary relative,” says Svante Pääbo, the project’s leader and director of genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. He notes that now scientists can begin to ask what genetically differentiates us from our closest living relative–the chimpanzee–and our closest extinct one.

So far, the answer to this question appears to be “not much.” According to the researchers, humans inherited anywhere from 1 to 4 percent of their genomes from Neanderthals; not only does the amount vary among individuals, but the actual location varies, too. “There’s no indication at this point that there was any particular gene with selective advantage that came in from Neanderthals,” says Richard E. Green, a biomolecular engineer at the University of California at Santa Cruz who was responsible for much of the genetic sequencing. “The signal appears to be widely distributed across the genome, and differs from individual to individual.”

Rather than focusing on the genes humans inherited, Green says, what’s more interesting are areas in the human genome where there is no Neanderthal signal whatsoever. “Those are intensely interesting because they suggest that something happened in our evolutionary history that wiped the slate clean.” Those genetic regions–and they’ve only found a relatively small number of them–are the ones that make us human. And a good percentage of those regions are already known to contain genes involved in skin and hair, brain function, and craniofacial morphology.

The group’s combined findings required an immense technological effort, one that spanned six years and multiple high-throughput sequencing technology platforms. It involved finding ways to differentiate Neanderthal DNA from modern human DNA contamination, eliminating microbial DNA that had invaded the bones, and determining how the Neanderthal sequences had chemically changed over time. But the ultimate result, says biological anthropologist John Hawks, of the University of Wisconsin, is “5.3 billion pieces of information about Neanderthals.” And that, he says, is something worth waiting for.

Before this paper, it seemed likely that the two groups had interbred, but there was no proof, says Hawks, who was not involved in the research. “And this study shows that what happened wasn’t like a one-night stand. Neanderthals are at least 1 percent and as much as 4 percent of your genome,” he says. “You’ve got 32 great-great-great-grandparents, and one of those is 3 percent of your genetics. This is what you’re talking about genealogically.”

Last month, University of New Mexico anthropologist Jeffrey Long and his colleagues spoke at a conference in which they presented data suggesting that patterns of genetic variation in contemporary people around the world could not be explained by the “out of Africa” founder group theory. “We mulled over different possible explanations, and saw that the ‘out of Africa’ migration alone could not explain the amount of variation we saw outside of Africa,” Long says. “And what we settled on as the most likely explanation was mixing with another archaic population.” In other words, the Neanderthals. Purely through genetic statistics, Long’s results implied a history that the Neanderthal genome can now confirm.

The results are shining a light into the dark period of human evolution that was previously inaccessible. “It’s super exciting–there’s just nothing in my career that has compared with this,” Hawks says.