Humans Picked Up Ancestral Immunity

Modern immune systems harbor signs of interbreeding with ancient hominins.

Aug 25, 2011
Kerry Grens

Reconstruction of a NeanderthalWIKIMEDIA, STEFAN SCHEER

Our ancestors' sexual relations with Neanderthals and the recently-discovered Denisovans might have shaped modern humans' ability to fight diseases. An international team of collaborators published evidence in Science this week that human immune genes are a mixture of Neanderthal, Denisovan, and ancestral human DNA—and that for some of these genes, archaic alleles are the majority.

“For 15 years there's been this idea that we all came out of Africa and nothing interesting came from Neanderthals, and it's sort of not true,” said John Hawks, an anthropology professor at the University of Wisconsin, who was not involved in this study. Recent genetic work has pointed to a history of modern human ancestors mating with Neanderthals—whose remains have been found in Europe and Asia—and the Denisovans of ancient Siberia, and the new study suggests that such interbreeding has shaped our current immune system, he said.

In total, researchers believe that one to six percent of our DNA is descended from interbreeding with archaic hominins that occurred tens of thousands of years ago. To determine whether alleles of human leukocyte antigen (HLA) genes, whose proteins help the body detect pathogens, were affected by the ancient encounters, post-doctoral researcher Laurent Abi-Rached of Stanford University and his colleagues scanned the genomes of three Neanderthals, one Denisovan (the only one identified so far), and several thousand modern humans from around the world. Sure enough, they found that modern humans carried several HLA alleles found in the Neanderthal and Denisovan genomes.

Possible archaic extent of HLA-A allele in modern humans. Red represents areas where archaic alleles are common, and blue are regions where archaic alleles are absent.Possible archaic extent of HLA-A allele in modern humans. Red represents areas where archaic alleles are common, and blue are regions where archaic alleles are absent.

 “A key finding is the presence of long haplotypes shared between archaic and modern humans, which is difficult to explain in any other way” than interbreeding, Abi-Rached told The Scientist. It's unlikely that these long stretches of DNA date back to the common ancestor of archaic and modern humans around 250,000 years ago, for example, because the HLA haplotypes diversify so quickly, he said.

While the presence of such archaic alleles was expected, their pervasiveness in modern genomes surprised Abi-Rached. For instance, in one gene, HLA-A, the archaic alleles comprised more than 50 percent of those in modern Europeans, more than 70 percent in Asians, and close to all of the HLA-A alleles in some Papua New Guineans.

Overall, the archaic alleles were more common among Europeans and Asians and less common among Africans, pointing to a likely influx of these alleles after modern humans left Africa and came into contact with Neanderthals and Denisovans. These findings fit in well with what's currently understood about interbreeding between modern humans and our archaic cousins, Svante Pääbo at the Max Planck Institute wrote in an email. In previous studies, “Neanderthal alleles tend to show up more in western Eurasia, and Denisovans more in Eastern Eurasia,” he said.

David Reich, a professor at Harvard Medical School, isn't totally convinced. The authors' claim that one of the alleles in modern humans, HLA-B*73, was passed down from Denisovans, showing evidence that the allele was picked up in western Asia after humans left Africa. But Reich and his colleagues’ genomic analysis did not find Denisovan DNA anywhere outside of the island countries of southeast Asia and Oceania.

This doesn't mean that Denisovan DNA can't be elsewhere, but “this raises the bar for me in terms of the evidence I would like to see to believe a claim of such a major impact of Denisovan genetic material on people in western Asia,” Reich wrote in an email to The Scientist.

Additionally, HLA-B*73 was not actually present in the DNA of the Denisovan that was sequenced. Thus, while the hypothesis that modern humans got this allele from Denisovans is reasonable, Hawks said, “it's not the same as having the smoking gun.”

L. Abi-Rached, et al., "The shaping of modern human immune systems by multiregional admixture with archaic humans," Science, doi:10.1126/science.1209202, 2011.