Modern humans are known to have interbred with Neanderthals, Denisovans and possibly other archaic hominins.
While genetically similar populations of Neanderthals are thought to have contributed approximately 2% to non-African genomes, Denisovan introgression has been observed to be more variable.
Particularly, Denisovan ancestry accounts for up to 5% of the genomes of the Indigenous peoples of Island Southeast Asia and Australia.
In addition, these components exhibit a deep divergence from the reference Altai Denisovan genome, providing strong evidence for the occurrence of multiple Denisovan introgression events across time and space.
To better understand the significance of this genetic contribution, University of Melbourne researcher Irene Gallego Romero and colleagues searched the genomes of 56 Papuan individuals to see if they carried Denisovan or Neanderthal DNA sequences, and then predicted how those sequences might affect the functioning of different types of cells.
Based on the location of the non-human sequences, the authors found that in Papuans, Denisovan DNA — but not Neanderthal DNA — appears to strongly and consistently affect immune cells and functions.
Further testing in cell cultures confirmed that Denisovan DNA sequences successfully regulated nearby genes, turning their expression up or down in ways that could affect how people respond to infections.
“We show that not only Neanderthal, but also Denisovan DNA is very likely to contribute to gene expression in human populations,” said 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.”
“Some of the Denisovan DNA that has persisted in Papuan individuals until today plays a role in regulating genes involved in the immune system,” Dr. Gallego Romero added.
“Our study is the first to comprehensively shed light on the functional legacy of Denisovan DNA in the genomes of present-day humans.”
The findings suggest that Denisovan DNA sequences altered the immune response in early modern humans living in New Guinea and nearby islands, potentially helping them adapt to their local environment.
“Our results suggest that Denisovan alleles segregating within modern human populations are also likely to actively participate in gene regulatory processes, especially those that take place within immune-related cells,” the researchers said.
“This agrees with recent findings from a study that analysed the genome of present-day people of Taiwan, the Philippines, the Solomon Islands and Vanuatu.”
“While further experimental validation of our observations is necessary in order to characterise the genome-wide impact of archaic introgression, or results argue for a potential contribution of Denisovan variants to immune-related phenotypes amongst early modern humans in the region, potentially favoring adaptation to the local environment.”
Study:
Denisovan introgression has shaped the immune system of present-day Papuans
Published: December 8, 2022
