Earlier this year, Kelso and collaborators identified a large stretch of Neanderthal DNA—143,000 DNA base-pairs long—that may have played a key role in helping modern humans fight off disease. The region spans three different genes that are part of the innate immune system, a molecular surveillance system that forms the first line of defense against pathogens. These genes produce proteins called toll-like receptors, which help immune cells detect foreign invaders and trigger the immune system to attack.
Modern humans can have several different versions of this stretch of DNA. But at least three of the variants appear to have come from archaic humans—two from Neanderthals and one from Denisovans. To figure out what those variants do, Kelso’s team scoured public databases housing reams of genomic and health data. They found that people carrying one of the Neanderthal variants are less likely to be infected with H. pylori, a microbe that causes ulcers, but more likely to suffer from common allergies such as hay fever.
Kelso speculates that this variant might have boosted early humans’ resistance to different kinds of bacteria. That would have helped modern humans as they colonized new territories. Yet this added resistance came at a price. “The trade-off for that was a more sensitive immune system that was more sensitive to nonpathogenic allergens,” said Kelso. But she was careful to point out that this is just a theory. “At this point, we can hypothesize a lot, but we don’t know exactly how this is working.”
Most of the Neanderthal and Denisovan genes found in the modern genome are more mysterious. Scientists have only a vague idea of what these genes do, let alone how the Neanderthal or Denisovan version might have helped our ancestors. “It’s important to understand the biology of these genes better, to understand what selective pressures were driving the changes we see in present-day populations,” Akey said.
A number of studies like Kelso’s are now under way, trying to link Neanderthal and Denisovan variants frequently found in contemporary humans with specific traits, such as body-fat distribution, metabolism or other factors. One study of roughly 28,000 people of European descent, published in Science in February, matched archaic gene variants with data from electronic health records. Overall, Neanderthal variants are linked to higher risk of neurological and psychiatric disorders and lower risk of digestive problems. (That study didn’t focus on adaptive DNA, so it’s unclear how the segments of archaic DNA that show signs of selection affect us today.)
At present, much of the data available for such studies is weighted toward medical problems—most of these databases were designed to find genes linked to diseases such as diabetes or schizophrenia. But a few, such as the U.K. Biobank, are much broader, storing information on participants’ vision, cognitive test scores, mental health assessments, lung capacity and fitness. Direct-to-consumer genetics companies also have large, diverse data sets. For example, 23andMe analyzes users’ genetics for clues about ancestry, health risk and other sometimes bizarre traits, such as whether they have a sweet tooth or a unibrow.