A major new study led by Yale University is helping to fill a long-standing gap in genetics research by providing one of the most comprehensive surveys to date of human genetic diversity in Oceania.
Although the South Pacific is home to a highly diverse population, people from this region have historically been underrepresented in large-scale genetic studies. Much of the genomics research has focused on populations of European descent, leaving important questions about human history and biology unanswered.
“Significant underrepresentation of Oceanians limits our understanding of human evolution and has the potential to further exacerbate health disparities as genomic research is used to develop new treatments,” said first author Selena Tucci, assistant professor of anthropology in the Yale School of Arts and Sciences and principal investigator at the Yale Institute for Human Evolutionary Genomics. “To fill that gap, my research team has embarked on a large-scale project to expand what is known about human genetic variation, including genetic variation inherited from extinct humans.”
Published in the June 11th magazine sciencethis research highlights how DNA inherited from extinct human relatives continues to influence modern human biology, health, and survival.
Oceania’s genome reveals ancient human history
To conduct the study, researchers sequenced the genomes of 177 people from 12 populations across the Southwest Pacific region, including Near Oceania, Papua New Guinea, the Bismarck Islands, and the Solomon Islands. They combined these data with 1,284 previously published genomes from populations around the world.
Researchers have uncovered new details about human evolution and adaptation by examining the genetic history of early people who settled the Pacific Ocean at least 45,000 years ago. Among the most shocking discoveries was evidence that the ancestors of the near-marine population interbred with at least three different groups related to the Denisovans, extinct human relatives first identified in fossil remains found in Siberia.
“Previous studies have shown that DNA inherited from extinct hominins such as Neanderthals and Denisovans survives, dispersed in the genomes of modern human populations,” Tucci said. “With this study, we were able to move beyond simply ‘resurrecting’ this DNA and show how it actively turns genes on and off. This is game-changing. This DNA is not just a remnant of an ancient relationship, but continues to influence our biology today.”
Denisovan DNA still influences human biology
Interbreeding between ancient humans and Denisovans left many genetic variations that remain in humans today, researchers say. Some of these variants continue to play functional roles in the human body.
To investigate its effects, the research team used an advanced genomic technique called a “massively parallel reporter assay.” This technology allows researchers to directly test how inherited genetic variations affect gene activity. The analysis identified more than 3,100 variants that alter gene expression.
The findings provide some of the strongest evidence to date that adaptive Denisovan genetic variants remain biologically active in modern humans.
Many of these variants were linked to the interferon-gamma signaling pathway, an important part of the immune system that helps protect the body from infections.
“DNA from extinct humans (Denisovans and Neanderthals) helped facilitate human adaptation to the diverse environments that people encountered as they migrated to this part of the world,” said Patrick Reilly, lead author of the study and an associate research fellow in the Yale School of Anthropology’s Institute for Human Evolutionary Genomics. “Pathogens represent one of the strongest selective pressures, or environmental factors, that affect our ability to survive throughout human evolution. We found evidence that genes inherited from Denisovans strengthened immunity to viruses and bacteria that ancient humans encountered in near Oceania.”
Ancient genes associated with immunity and skeletal development
The study also found evidence that Denisovan DNA contributed to skeletal development. Researchers have identified an adaptive Denisovan variant of a gene known as TRPS1.
Interestingly, the same genes have undergone strong positive selection in hunter-gatherers in the Central African rainforest and in highland populations of Ecuador. This discovery shows how evolution repeatedly promotes similar adaptations in different populations living in very different parts of the world.
“Although Denisovans disappeared from the earth thousands of years ago, this study proves that our histories are still deeply intertwined,” Tucci said.
Co-authors of the study include Daniela Tejada Martinez, Samantha L. Miller, Audrey Chajadi, Zhang Liu, and Alisa Pomar of the Yale Institute for Human Evolutionary Genomics. Stephen Rong, Jared Akers, Margaret E. Prentice, and Steven K. Reilly of Yale School of Medicine; D. Andrew Meriwether of Binghamton University; Francoise R. Friedlender and Jonathan S. Friedlender of Temple University; George Koki of the Papua New Guinea Medical Research Institute.
Funding for the study was provided by the National Institute of General Medical Sciences and the National Human Genome Research Institute of the National Institutes of Health.
