Ancient gene influences immunity of First Nations Peoples of Oceania microbiologystudy

An ancient gene mutation among First Nations inhabitants of Oceania may make them more susceptible to infectious diseases like influenza, according to a new study by scientists at the University of Colorado Anschutz Medical Campus.

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

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

The researchers traced the allele, a variant of a gene that arises from a mutation, to the “archaic people” or Denisovans who diverged from modern humans before eventually going extinct.

Scientists believe the First Nations inhabitants 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. That’s where researchers believe they picked up the allele.

It’s known as KIR3DLI*114 and the study said it is widespread and unique to Oceania as an allele derived from these archaic people. They suspect it may affect the body’s immune response to infection, among factors accounting for the severity and poor outcomes of infectious diseases among First Nations peoples across Oceania.

“Likely following emigration out of Africa, present day First Nations Oceanians diverged from Eurasians,” the study said. “Subsequent admixture with archaic humans introduced new genetic material, having major impact on genes of the immune system.”

The scientists studied the immunogenic composition of this group and identified “a unique and divergent form of KIR3DL1” with characteristics of archaic human genetic sequences. Then they investigated the origin, distribution and functions of the allele to determine if it impacted the course of natural killer (NK) cell-driven immunity across Oceania.

Norman said the allele likely offered immuno-protection at some point but now may make First Nations peoples more susceptible to certain infectious diseases and other ailments.

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

The study found up to 30% of First Nations individuals in Oceania carry this allele or about five million people.

The implications are wide-ranging for innate and adaptive immunity, autoimmunity, cancer, immunotherapy and neurological disease. The study shows the direct impact of archaic genetics on First Nations peoples of Oceania.

“This is the first real demonstration of a really clear function of one of these archaic genes,” Norman said. “The bigger picture is that we are using these methods to study these populations with the goal of addressing health disparities today and treating diseases across the populations.”

Norman noted that this real-world 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 the participants for their contribution to this unique study.”