Some of the most Neandertal-rich regions of the modern human genome are those that contain immune system genes. There’s a good reason for that. “Of all the challenges, forces and threats humans have faced over the course of evolution, pathogens have been one of the greatest,” says Lluis Quintana-Murci, a population geneticist at the Pasteur Institute in Paris.
Genes involved in the body’s first line of defense against pathogens are under strong
evolutionary pressure not to change, Quintana-Murci and colleagues report in the Jan. 7
American Journal of Human Genetics. Some of the genes under the strongest pressure are Toll-like receptor genes
TLR1,
TLR6 and
TLR10. Mutations in those genes, which help detect pathogens and coordinate inflammatory responses, could lead to severe, life-threatening diseases, he says.
But there’s a conundrum: In modern humans, these genes would have had to change to deal with new pathogens that humans encountered outside of Africa. It would have taken humans thousands of years to build up the right mutations. Interbreeding with Neandertals may have provided a shortcut to immunity without risking life-threatening mutations, Quintana-Murci surmises. Neandertals had been living with European pathogens for hundreds of thousands of years, gradually accumulating helpful tweaks to ward off the pathogens, but to not overreact and produce strong inflammation that could kill an infected person, he says. Those
TLR genes were some of those most often inherited from Neandertals, the researchers found.
“Perhaps spending a night or two with a Neandertal was a small price to pay for getting thousands of years of genetic adaptation,” Capra said at the AAAS press briefing.
Kelso’s group took a closer look at what the ancient genes are doing for present-day people. The Neandertal versions don’t change the
TLR genes themselves, but change activity of the genes, Kelso’s group discovered. The
TLR genes are more active in people with Neandertal core haplotype III. Those people are less likely to get infected with the ulcer-causing
Helicobacter pylori bacterium. But the advantage comes with a cost: Those people are more prone to allergies, the researchers found.
“We can’t really blame Neandertals for all the diseases we have,” Capra said, but, on the whole, the ancient DNA probably isn’t doing modern people much good.
