First, Enard systematically combed the scientific literature to compile a list of 4,534 human proteins that interact with modern viruses such as influenza, HIV, and hepatitis. Viruses evolve to have very specific interactions with the proteins of cells they infect. A flu virus might, for example, fit like a key into the “lock” of a cell-surface protein, tricking the human cell into letting it in. But modify that lock slightly and the virus will no longer fit; in other words, that cell is now resistant.

Enard reasoned that Neanderthals had evolved some resistance to the viruses that must have circulated among them in Europe. Modern humans, on the other hand, were likely encountering those viruses for the first time. So when they mated with Neanderthals, subsequent generations of offspring that inherited the genes for Neanderthal-virus–interacting proteins would be more likely to survive. Other scientists have identified segments of Neanderthal DNA in humans that likely served some evolutionary advantage, so Enard compared those with his list of 4,534 virus-interacting proteins. Indeed, he found that genes for virus-interacting proteins were enriched in the DNA of Neanderthal origin.

Scientists are stunned by a Neanderthal hybrid discovered in a Siberian cave.

Of course, it should work the other way, too. Modern humans likely brought their own human viruses with them, and human-virus–interacting proteins would have had to be selected for in Neanderthals. There are no living Neanderthals, but scientists had previously sequenced the 50,000-plus-year-old genome of a Neanderthal man found in Siberia, who had stretches of modern-human DNA, suggesting a human ancestor. You can’t draw sweeping conclusions from just one individual, but Enard found that the longer remnants of human DNA in this Neanderthal man also matched up with human-virus–interacting proteins—proteins that may have protected his ancestors from human viruses.

The findings fit in nicely with previous research that found immune-related genes are common in stretches of Neanderthal DNA that persist in humans. “Pathogens have been a big driver in human adaptations,” says Emilia Huerta-Sanchez, a population geneticist at Brown University.

There were also unexplained patterns in the Neanderthal and human DNA. Viruses come in two big groups, ones whose genetic material is encoded in DNA (such as adenoviruses and smallpox) and ones whose genetic material is encoded in RNA (flu, yellow fever, HIV, etc.). Enard found that it was specifically Neanderthal genes that code for RNA-virus–interacting proteins that are most likely to remain in the human genome—but only among Europeans, not East Asians. Other research has suggested that the ancestors of Europeans and East Asians likely had separate histories of interbreeding with Neanderthals.