When modern humans first migrated from Africa to the tropical islands of the southwest Pacific, they encountered unknown people and new pathogens. But their immune systems may have learned a few survival tricks when they mated with the locals – the mysterious Denisovans who gave them immune gene variants that could have protected the newcomers’ offspring against local diseases. Some of these variants still persist today in the genome of people living in Papua New Guinea, according to a new study.
Researchers have known for a decade that people in Papua New Guinea and other parts of Melanesia, a subregion in the southwest Pacific Ocean, inherited up to 5% of their DNA from Denisovans. , ancient humans closely related to Neanderthals who arrived in Asia around 200,000 years ago. years ago. Scientists speculate that these variants have benefited people in the past – perhaps by helping modern humans better ward off local diseases – but they have wondered how this DNA could still alter people’s appearance, actions and feelings. people today. However, it has been difficult to detect the function of Neanderthal and Denisovan DNA in Melanesians because scientists have analyzed so little genetic data from humans living in Papua New Guinea and other parts of Melanesia.
The new study overcomes this problem by using genetic data from 56 individuals from Papua New Guinea that was recently analyzed for another paper, as part of the Indonesian Genome Diversity Project. The researchers, mainly from Australia and New Guinea, compared these genomes with those of Denisovans from Denisova Cave in Siberia, as well as with Neanderthals. They found that Papuans had inherited unusually high frequencies of 82,000 genetic variants known as single nucleotide polymorphisms, which result from single base or letter differences in the Denisovans’ genetic code.
The team then searched for these variants in a database that links genes to various functions in different tissues in humans. They focused on gene variants related to the immune system that could promote or enhance protein production of a neighboring gene, for example, or stop or attenuate its function. These adjustments can help optimize an immune system for specific pathogens in its environment; an overly strong immune response can be as deadly as the infection itself.
Among Papuans, scientists have found many Denisovan variants located near genes known to impact human immune responses to viruses and other pathogens, such as influenza and chikungunya. Next, they tested the function of eight variants of the Denisovan gene associated with the expression of proteins produced by two genes in particular, OAS2 and OAS3, ‘lymphoblastoid’ — cell lines of B lymphocytes, a type of white blood cell that produces antibodies essential for the body’s immune response. These cell lines were collected from Papuans by study co-author Christopher Kinipi, a Papuan physician and director of health services at the University of Papua New Guinea.
Two of Denisovan’s genetic variants found in these Papuan cell lines reduced the transcription or production of proteins that regulate cytokines, part of the immune system’s defense against infection, reducing inflammation. This moderate inflammatory response could have helped the Papuans cope with a wave of new infections they would have encountered in the region.
“One of the strengths of the study is that they tested the Denisovan variants in Papuan cell lines, which is essentially the cellular environment in which they evolved,” says functional genomics Francesca Luca de la Wayne. State University, which was not part of the study.
Taken together, these experiments suggest that these Denisovan gene variants “could fine-tune the immune response” to optimize it to its environment, says human evolutionary geneticist Irene Gallego Romero of the University of Melbourne, lead author of the new study published in PLOS genetics. “In the tropics where people have high infectious disease loads, you might want to tone down the immune response a bit and not go overboard.”
These findings are consistent with previous work on the role of Neanderthal variants in living Europeans. According to computational biologist Janet Kelso of the Max Planck Institute for Evolutionary Anthropology. The study shows that this type of gene exchange was “an important mechanism for how humans adapted quickly [to new challenges]especially pathogens,” says human geneticist Luis Barreiro from the University of Chicago.
But he would like to see future work testing whether Denisovan gene variants actually give Papuans a better chance of warding off or surviving specific illnesses.
Overall, this study shows that “matings that took place tens of thousands of years ago still influence the biology of contemporary individuals,” says population geneticist Joshua Akey of Princeton University.
#Mysterious #ancient #humans #people #Papua #Guinea #immune #edge