A major new study led by Yale University is helping fill a longstanding gap in genetics research by providing one of the most comprehensive examinations yet of human genetic diversity in Oceania.
Although the South Pacific is home to extraordinarily diverse populations, people from this region have historically been underrepresented in large genetic studies. Much of genomics research has focused on populations of European ancestry, leaving important questions about human history and biology unanswered.
“The drastic underrepresentation of Oceanians limits our understanding of human evolution and could exacerbate health inequalities as genomic research is used to develop novel medical treatments,” said lead author Serena Tucci, assistant professor of anthropology in Yale’s Faculty of Arts and Sciences and principal investigator of the Yale Human Evolutionary Genomics Laboratory. “To fill that gap, my research team embarked on a large-scale project to expand what is known about human genetic variation, including genetic variants inherited from extinct hominins.”
Published June 11 in the journal Science, the research highlights how DNA inherited from extinct human relatives continues to influence modern human biology, health, and survival.
Oceania Genomes Reveal Ancient Human History
To conduct the study, researchers sequenced the genomes of 177 people from 12 populations across Near Oceania, the southwestern Pacific region that includes Papua New Guinea, the Bismarck Archipelago, and the Solomon Islands. They combined these data with 1,284 previously published genomes from populations around the world.
By examining the genetic history of some of the earliest people to settle the Pacific, who arrived in the region at least 45,000 years ago, the team uncovered new details about human evolution and adaptation. Among the most striking findings was evidence that the ancestors of Near Oceanic populations interbred with at least three distinct groups related to Denisovans, an extinct human relative first identified from fossil remains discovered in Siberia.
“Previous studies showed that DNA inherited from extinct hominins, such as Neanderthals and Denisovans, survives, scattered, in the genomes of present-day human populations” Tucci said. “With this study we have moved beyond simply ‘resurrecting’ this DNA to showing how it actively turns genes on and off, which is game-changing. This DNA is not just a remnant of ancient liaisons; it continues to influence our biology today.”
Denisovan DNA Still Influences Human Biology
According to the researchers, interbreeding between ancient humans and Denisovans left behind many genetic variants that remain present in people today. Some of these variants continue to play functional roles in the human body.
To investigate their effects, the team used an advanced genomic method called a “massively parallel reporter assay.” This technique allowed researchers to directly test how inherited genetic variants affect gene activity. The analysis identified more than 3,100 variants that alter gene expression.
The findings provide some of the strongest evidence yet that adaptive Denisovan genetic variants remain biologically active in modern humans.
Many of these variants were linked to the interferon-gamma signaling pathway, a key part of the immune system that helps protect the body against infectious diseases.
“DNA from extinct hominins — Denisovans and Neanderthals — helped facilitate human adaptation to diverse environments that people encountered as they migrated into this region of the world,” said Patrick Reilly, first author of the study and associate research scientist in the Yale Human Evolutionary Genomics Laboratory in the Department of Anthropology. “Pathogens are one of the strongest selective pressures — environmental factors that affect our ability to survive — throughout human evolution. We find evidence that genes inherited from Denisovans bolstered immunity to viruses and bacteria ancient humans encountered in Near Oceania.”
Ancient Genes Linked to Immunity and Skeletal Development
The study also found evidence that Denisovan DNA contributes to skeletal development. Researchers identified adaptive Denisovan variants in a gene known as TRPS1.
Interestingly, the same gene has experienced strong positive selection in central African rainforest hunter-gatherers and in highland populations of Ecuador. The finding illustrates how evolution can repeatedly favor similar adaptations in different populations living in very different parts of the world.
“While Denisovans vanished from the Earth thousands of years ago, this research proves that our histories remain deeply intertwined,” Tucci said.
The study’s coauthors include Daniela Tejada-Martinez, Samantha L. Miller, Audrey Tjahjadi, Chang Liu, and Alysa Pomer of the Yale Human Evolutionary Genomics Laboratory; Stephen Rong, Jared Akers, Margaret E. Prentice, and Steven K. Reilly of Yale School of Medicine; D. Andrew Merriwether of Binghamton University; Françoise R. Friedlaender and Jonathan S. Friedlaender of Temple University; and George Koki of Papua New Guinea Institute for Medical Research.
Funding for the research was provided by the National Institute of General Medical Sciences and the National Human Genome Research Institute of the National Institutes of Health.