Ancient Denisovan DNA Still Shapes Human Immunity Today

A major Yale-led study addresses the long-standing underrepresentation of Oceanian populations in genomics research, offering new insight into human evolution. Published in Science, the work sequenced genomes from 177 individuals across 12 populations in Near Oceania—including Papua New Guinea, the Bismarck Archipelago, and the Solomon Islands—and combined them with 1,284 previously published genomes. The results show that the ancestors of these populations, who settled the region at least 45,000 years ago, interbred with at least three distinct Denisovan-related groups.

Using a technique called a massively parallel reporter assay, researchers directly tested how inherited Denisovan genetic variants affect gene expression, identifying more than 3,100 variants that alter gene activity. Many of these are linked to the interferon-gamma signaling pathway, a core component of immune defense against pathogens—providing some of the strongest evidence yet that DNA from an extinct human relative remains functionally active in living humans.

The study also found adaptive Denisovan variants in the TRPS1 gene, tied to skeletal development. Notably, the same gene shows strong positive selection in Central African rainforest hunter-gatherers and highland populations in Ecuador, illustrating how evolution can independently favor similar adaptations across very different environments.

For engineers working in genomics and bioinformatics, the findings matter on two fronts: they broaden genomic reference data by including historically underrepresented populations—key for equitable future medical genomics—and they show that functional assays can directly measure the biological impact of ancient DNA variants, not just detect their presence.