Denisovan DNA May Have Shaped Immune Systems in Papua New Guinea

People living in Papua New Guinea today may have inherited genetic variants from an ancient group of humans called Denisovans. And these variants could affect their immune systems, a new study finds.

Denisovans and their sister species Neanderthals went extinct thousands of years ago. But the ancestors of modern humans mated with both of these groups, exchanging DNA.

“Matings which took place tens of thousands of years ago are still influencing the biology of contemporary individuals,” Joshua Akey, a population geneticist at Princeton University who did not contribute to the study, tells Science’s Ann Gibbons.

Previous research revealed that Neanderthal DNA inherited by modern humans may influence the risk of developing diabetes or severe Covid-19. It might also play a role in smoking and alcohol consumption, as well as the development of celiac disease.

Up to 5 percent of Papuans’ DNA comes from Denisovans, per the new paper, published this month in the journal PLOS Genetics. But scientists understand less about how Denisovan DNA influences modern humans, in part because the DNA of Papuans and other people in the southwest Pacific region has been understudied.

“The human genetic datasets that have been used to understand Neanderthal DNA or to link it to phenotypes have mostly come from people of European ancestry … and not so much anyone else,” Irene Gallego Romero, a human evolutionary biologist at the University of Melbourne in Australia who led the study, tells Inverse. “Denisovan DNA is missing from [genomic datasets]; it’s missing from the U.K. Biobank, which is where you would go to work out what a [gene] does.”

In the new study, the researchers looked at the genomes of 56 Papuans. They found that the genomes contained a high number of mutations inherited from Denisovans, many of which were located close to genes that influence humans’ immune response.

Next, the researchers grew cells in a lab with some of the same mutations. Two of these mutations influenced the activity of immune genes.

“There are still only rather few studies that have looked specifically at the effect of Denisovan DNA in present-day people in Oceania and Island Southeast Asia, so this is a nice addition,” Janet Kelso, a computational biologist at the Max Planck Institute for Evolutionary Anthropology in Germany who did not contribute to the research, tells Inverse’s Miriam Fauzia in an email.

Gallego Romero tells Inverse that DNA from Denisovans might have allowed modern humans’ ancestors to better fight against pathogens in new environments.

“When you think of humans walking around this part of the world 60,000 years ago, one of the biggest challenges is encountering new pathogens that could wipe you out,” she says to Scientific American’s Freda Kreier.

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Will Sullivan is a science writer based in Washington, D.C. His work has appeared in Inside Science and NOVA Next.