Ancient Denisovan DNA found to have shaped the immune system of modern Papuans

The DNA of Denisovans likely helped the evolution of modern Papuans’ immune systems.

Closely related to Homo neanderthalensis (Neanderthals), Denisovans were discovered in 2010 and are only known to science through their DNA and sparse remains in Siberia and Tibet. Denisovans, like Neanderthals, are mysterious ancient humans who went extinct but appear to have interbred with ancient modern humans, Homo sapiens.

Denisovans may have lived until as recently as 30,000 years ago.

It’s believed that Denisovans and Neanderthals shared a common ancestor about 400,000 years ago. While Neanderthals went to Europe, the Denisovans split eastward into Asia.

Today, Denisovan DNA makes up about five percent of the DNA of Papuans, indigenous Australians, Melanesians and other ethnic groups in Southeast Asia such as in the Philippines. Similarly, Neanderthals contributed 1-4 percent of non-African human genomes, depending on the region of the world.

As little as 40,000 years ago, modern humans had 6-9 percent Neanderthal DNA.

Read more: Denisovan DNA may have aided Pacific migration

Australian and Papuan researchers sought to better understand the significance of Denisovans’ genetic contributions to modern human populations. Their results are published in the journal PLOS Genetics.

The scientists mapped and analysed the genomes of 56 modern Papuans to see if they carried any bits of Denisovan or Neanderthal DNA. They then predicted how the sequences given to the Papuans by the ancient humans might affect the function of different cell types.

A portrait of a juvenile female Denisovan based on a skeletal profile reconstructed from ancient DNA methylation maps. Credit: Maayan Harel.

Looking at where the genes appeared to not come from ancient Homo sapiens, the team found that Papuans had Denisovan – not Neanderthal – DNA which strongly and consistently affected immune cells and their functions.

Further testing of cell cultures confirmed this. Denisovan DNA sequences influenced nearby genes, either making them more or less pronounced in ways that could affect how the human body responds to infections.

The study suggests that the DNA passed down from Denisovans may have helped early modern humans living in New Guinea and nearby islands by altering their immune response and helping them adapt to their environment.

“Some of the Denisovan DNA that has persisted in Papuan individuals until today plays a role in regulating genes involved in the immune system,” explains senior author Dr Irene Gallego Romero from the University of Melbourne. “Our study is the first to comprehensively shed light on the functional legacy of Denisovan DNA in the genomes of present-day humans.”

Exploring how DNA from now extinct humans plays into gene expression may be key in understanding the consequences of interbreeding between early modern humans and other groups such as Neanderthals and Denisovans.

Read more: Denisovan DNA found in human genomes

The results of the study support the theory that ancient DNA from long-gone human groups has impacted genetic diversity and evolution in modern human. Multiple characteristics of modern people can likely be traced back to Denisovan and Neanderthal DNA.

“We show that not only Neanderthal, but also Denisovan DNA is very likely to contribute to gene expression in human populations,” says first author Dr Davide Vespasiani also from the University of Melbourne. “Further validations will reveal whether these effects are mostly cell type specific or consistent across cells.”

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