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 examinations to date of human genetic diversity in Oceania.
Although the South Pacific is home to an exceptionally diverse population, people in the region have historically been underrepresented in large genetic studies. Most genomics research has focused on populations of European ancestry, leaving important questions about human history and biology unanswered.
“The underrepresentation of Oceanic peoples limits our understanding of human evolution and may exacerbate health disparities 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 began a large-scale project to expand what is known about human genetic variation, including genetic variants inherited from extinct hominins.”
Published in the journal on June 11 ScienceThe research sheds light on how DNA inherited from extinct human relatives affects modern human biology, health and survival.
Oceania genome reveals ancient human history
To conduct the study, researchers sequenced the genomes of 177 people from 12 populations in 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 in the Pacific Ocean, who arrived in the region at least 45,000 years ago, the team uncovered new details about human evolution and adaptation. One of the most surprising findings was evidence that the ancestors of Nearctic populations had interacted with at least three different groups related to the Denisovans, an extinct human relative first identified from fossil remains discovered in Siberia.
“Previous studies have shown that DNA inherited from extinct hominins such as Neanderthals and Denisovans survives scattered in the genomes of current human populations,” Tucci said. “With this study we have moved beyond simply ‘reviving’ this DNA to showing how it actively turns genes on and off, which is game-changing. This DNA is not just a relic of ancient relationships; it is still influencing our biology today.”
Denisovan DNA still influences human biology
According to researchers, interbreeding between ancient humans and Denisovans left many genetic variants that still exist in people today. Some of these types 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 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, a key part of the immune system that helps protect the body from infectious diseases.
“The DNA of extinct hominins – Denisovans and Neanderthals – helped facilitate human adaptation to the diverse environments that people encountered when they migrated to this region of the world,” said Patrick Reilly, the study’s first author and associate research scientist at the Yale Human Evolutionary Genomics Laboratory in the Department of Anthropology. “Pathogens are one of the strongest selective pressures – environmental factors that influence our ability to survive throughout human evolution. We find evidence that genes inherited from Denisovans strengthened immunity to viruses and bacteria found in ancient humans near Oceania.”
Ancient genes linked to immunity and skeletal development
The study also found evidence that Denisovan DNA contributes to skeletal development. Researchers identified an adaptive Denisovan variant in a gene called TRPS1.
Interestingly, this same gene has experienced strong positive selection in Central African rainforest hunter-gatherers and Ecuadorian highland populations. The discovery shows how evolution can repeatedly favor similar adaptations in different populations living in different parts of the world.
“Although Denisovans disappeared from Earth thousands of years ago, this research proves that our history is deeply interconnected,” Tucci said.
Study co-authors include Daniela Tejada-Martinez of the Yale Human Evolutionary Genomics Laboratory, Samantha L. Miller, Audrey Tajhazadi, Chang Liu and Alyssa Pommer; Stephen Rong, Jared Akers, Margaret E. Prentice, and Steven K. of Yale School of Medicine. Reilly; D. Andrew Meriwether of Binghamton University; Temple University’s Francois R. Friedlaender and Jonathan S. Friedlaender; and George Koki of the 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.