If you suffer from hayfever in spring or food allergies, you might want to blame a Neanderthal or Denisovan ancestor. The interspecies mating that accounts for a small proportion of our genome has given some people a hyper-alert immune system, providing extra protection at the cost of overreacting to harmless pollen or foods.
People of European descent have inherited between 1 and 6 percent of their genome from Neanderthals, although the circumstances under which the mating occurred remain unknown. In July, Dr. Michael Dannemann of the Max Planck Institute for Evolutionary Anthropology presented evidence at the Society for Molecular Biology and Evolution conference that this inheritance is particularly common in DNA controlling Toll-like receptors (TLRs), proteins that initiate the body's response to potential dangers.
Both Dannemann and Dr. Lluis Quintana-Murci of the Institut Pasteur, lead author of the second paper, conclude that the Neanderthal versions of TLRs are expressed more strongly, producing stronger immune responses.
"We found that interbreeding with archaic humans – the Neanderthals and Denisovans – has influenced the genetic diversity in present-day genomes at three innate immunity genes belonging to the human Toll-like-receptor family,” said Janet Kelso, one of Dannemann's coauthors, in a statement. The variations or alleles in question associated with TLR1 and TLR6 come from Neanderthals. A TLR10 allele resembles those seen in Denisovans, the mysterious third group of humans that lived in Siberia and interbred with both modern humans and Neanderthals.
"These, and other, innate immunity genes present higher levels of Neanderthal ancestry than the remainder of the coding genome," said Quintana-Murci.
For Quintana-Murci the work on the three TLRs was just one part of a project studying the evolution of genes for immunity. The paper also reports that for the immune system, “most adaptations targeting coding variation have occurred in the last 6,000 to 13,000 years, the period at which populations shifted from hunting and gathering to farming.”
Dannemann and Kelso, on the other hand, were investigating our genetic inheritance from extinct human species, finding that the TLR genes show unusually high frequency of alleles that resemble those of the Neanderthal and Denisovan peoples. In one case, between 11 and 51 percent of non-African people, with large differences by ethnicity, have a Neanderthal-like allele, far above the typical 1.5 to 2.1 percent inherited from these sources.
The frequency of Neanderthal-like DNA (orange or green) for TLRs by region of origin. Dot size is proportional to the number of individuals sampled. Credit: Dannemann et al./American Journal of Human Genetics 2016
Since infectious diseases have been such a frequent cause of death for humans, particularly prior to the development of antibiotics and vaccines, the immune system has been under intense selective pressure – people with weak immune systems seldom got to pass on their genes, so beneficial genes from rare inter-species mating flourished.
"Neanderthals... had lived in Europe and Western Asia for around 200,000 years before the arrival of modern humans,” Kelso said. “They were likely well adapted to the local climate, foods, and pathogens. By interbreeding with these archaic humans, we modern humans gained these advantageous adaptations." As evidence for this advantage, Dannemann and Kelso found that people with the alleles from other species were less likely to have the Helicobacter pylori bacterium, which causes stomach ulcers.
Had the Neanderthal versions of TLR1 and TLR6 been entirely beneficial, it is likely they would have come to dominate human genetics. However, the inheritors of those genes pay a price for their immune protection in greater susceptibility to allergies, which is probably why multiple forms of these genes survive to this day.