Study: Denisovans May Have Passed Immune Properties to Modern-day Indonesians

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Researchers have made unparalleled gains in genomic research in the past decade as instrumentation simultaneously became more advanced and cost-effective. Instead of sequencing a human genome for about $200,000 in 2009, it can now be done across a myriad of labs for less than $1,000.

However, despite the fact that Island Southeast Asia accounts for nearly 6 percent of the world’s population, almost every genomic study has focused on those of European descent.

“Most of the world is deeply understudied. As we move further into the age of personalized and genomic medicine, understanding how genetics drives disease-risk across diverse populations is crucially important,” said Heini Natri, a postdoctoral fellow at The Translational Genomics Research Institute, and lead author of a new study that is the first to characterize genes across distinct populations in Indonesia.

The study, published in PLOS Genetics, studied genomic diversity among 116 individuals from three Indonesian populations: the Mentawai on the west coast of Sumatra; the Sumba in central Indonesia; and the Korowain from the western side of the isle of New Guinea.

The Korowain are hunter-gatherers who live in an ecological area akin to a rainforest, while the inhabitants of Sumba and Mentawai are village-based agriculturists. Unlike Mentawai, though, Sumba has a low population density and little contact between its villages.

Study results suggest there is low genetic diversity among those who live on each island, and even in each village, but also high genetic diversity among people from island to island, leading the authors to hypothesize that environmental pressures from each unique location are to blame.

“[These locations] have resulted in small, isolated populations of a few hundred to a few thousand individuals that can be identified genetically between villages roughly 10 km apart, making it a near unique study system for examining gene-by-environment interactions,” the study reads.

While genes were expressed differently among most location comparisons, the largest differences were seen when comparing the Sumbanese or Metawai with the Korowai. That’s because the DNA of Korowai persons holds the world’s last remaining remnants of genetic code—as much as 5%—from Denisovans, a cousin of modern humans. The genes involved with immune function were the most distinct, suggesting both an adaptive response to local environmental pressures, such as tropical diseases, as well as the age-old influence of Denisovans.

“Indeed, our data suggest that Denisovan introgression in New Guinea may be impacting gene expression levels in the Korowai. More broadly, Indonesia is an epicenter of infectious disease diversity, such as malaria and other emerging tropical diseases. Immune pressure from infectious diseases are responsible for some of the strongest selective forces on humans throughout our species' evolutionary history, and Indonesia offers unique advantages for studying responses to these diseases,” said Natri.

The researchers are continuing their study, integrating more genetic data, exploring patterns of local ancestry and investigating how archaic human genes manifest in modern-day populations.

“We are now attempting to pinpoint individual genetic changes, in particular, those that are carried over in these remnant DNA fragments from Denisovans, which regulate how much or how little a gene is turned on, and how these genetic changes may shape immune response,” said Natri.