An ancient gene affects the immunity of indigenous peoples of Oceania

“We found a fairly diverse set of genes in this population, but there was one allele that really stood out in terms of genetic makeup,” said lead study author Paul Norman, Ph.D., professor of biomedical informatics at the University of Colorado School of Medicine. . “We did some research and suspect that this allele is of archaic human origin.”

The study was published today in the journal Cell in collaboration with researchers from Australia, Papua New Guinea, Mexico and the UK.

The researchers traced the allele, a gene variant that results from mutation, to “archaic humans,” or Denisovans, who diverged from modern humans before eventually going extinct. Scientists believe that the indigenous people of Australia, New Guinea, American Samoa, New Caledonia, the Solomon Islands and other parts of Oceania encountered and interbred with Denisovans after leaving Africa and traveling through Europe and Eurasia. This is where the researchers believe they picked up the allele.

It is known as KIR3DLI*114, and the study found that it is widespread and unique to Oceania, being an allele derived from these archaic humans. They suspect this may affect the body’s immune response to infection, among factors explaining the severity and poor outcomes of infectious diseases among indigenous peoples across Oceania.

“It is likely that after emigration from Africa, the modern indigenous peoples of Oceania separated from the Eurasians,” the study says. “Subsequent interbreeding with archaic humans resulted in new genetic material that had a profound effect on immune system genes.”

The scientists examined the immunogenic composition of this group and identified a “unique and divergent form of KIR3DL1” with characteristics of archaic human genetic sequences. They then examined the origin, distribution and function of the allele to determine whether it influences the course of killer (NK) cell-driven immunity in Oceania.

Norman said the allele likely provided immune protection at one point, but may now make Indigenous people more susceptible to certain infectious diseases and other ailments.

“It must have once had protective properties, and we want to see what that is,” he said.

The study found that up to 30% of Oceania’s indigenous peoples are carriers of this allele, or about five million people.

The implications of this are wide-ranging for innate and adaptive immunity, autoimmunity, cancer, immunotherapy, and neurological diseases. The study shows the direct influence of archaic genetics on the indigenous peoples of Oceania.

“This is the first real demonstration of a really clear function for one of these archaic genes,” Norman said. “More broadly, we are using these methods to study these populations with the goal of eliminating today’s health disparities and treating disease across populations.”

Norman noted that this case study represents “our comprehensive collaboration with immunologists and infectious disease experts from the University of Melbourne, Australia, and Oxford, UK, structural biologists from Monash University, and Indigenous health researchers from Charles Darwin and Queensland Universities in Australia. We are very grateful to all participants for their contributions to this unique study.”