DNA study reveals how mysterious missing human shaped our immune system

DNA study reveals how mysterious missing human shaped our immune system

In the summer of 2008, in a cave nestled in the Altai Mountains in Siberia, Russian scientists have unearthed a finger bone fragment. At first, scientists assumed the fossil was from a Neanderthal – the cave was a known treasure trove of stone artifacts left behind by our thick-browed ancestors. But it was not until a genetic analysis carried out in 2010 that the scientific community realized that it was an entirely different prehistoric human species: the Denisovans.

Since then, we’ve learned more about our mysterious cousins ​​- their namesake comes from the Denisova cave in which the bone fragment was found – and that early humans definitely passed third base when the two hominins interacted there. is tens of thousands of years old. People throughout Asia carry Denisovan DNA, with the highest concentration among individuals living in the Pacific island region of Melanesia (around four to six percent, by some estimates). While Neanderthal DNA is linked to a range of physical and personality traits, not to mention illnesses like diabetes and Covid-19, the influence of Denisovan DNA in our modern times is not all. quite clear.

But according to a study published Thursday in the journal PLOS genetics, we may be closer to an answer, one that resides in the human immune system. A group of researchers led by the University of Melbourne in Australia found that for indigenous people on the island of New Guinea, Denisovan DNA appeared to regulate genes and immune cells more consistently and with greater great influence than Neanderthal DNA. Researchers suspect that this feature helped Papuans adapt to their local environment and fight off infectious diseases, and it may have implications for some immune system-related diseases affecting Papuans today.

“It’s really nice to see a new study on the effects of Denisovan’s DNA in today’s Papuans,” said Janet Kelso, a computational biologist at the Max Planck Institute for Evolutionary Anthropology in Germany, who did not participate in the study. Reverse in an email. “There are still only a few studies that have looked specifically at the effect of Denisovan DNA in people today in Oceania and insular Southeast Asia, so it’s a nice addition.”

How they did — The researchers took a large dataset that had sequenced the genomes of more than 300 individuals from Indonesia and Papa New Guinea, all of whom had Denisovan and Neanderthal DNA. This dataset, published in 2019, had sorted out which genes were associated with which archaic hominin but it had not determined, for Denisovan, exactly the functional role of DNA.

Looking at the genomes of 56 Papuans from this dataset, Irene Gallego Romero, a human evolutionary biologist at the University of Melbourne who led the study, and her team compared Denisovan’s DNA to a another National Institutes of Health database called Roadmap Epigenomics, a public catalog of which genes are active in which cell types (essentially, the genes that define a cell’s function and other characteristics).

What they found – Gallego Romero and his colleagues found that Denisovan DNA in Papuans, more so than Neanderthal DNA, tended to fall into regions of the genome that don’t actually make any proteins – called non-coding regions. Despite the name, that doesn’t mean these sequences aren’t important.

“Two percent of the genome is actually [involved] in protein coding,” says Gallego Romero Reverse. “The rest is what used to be called junk DNA, but it’s not junk food. Its function is mainly to control how much of a gene you express, when you express it, and what cell types respond to which stimulus.

And consistently, researchers have seen these non-coding Denisovan gene sequences appear most active in immune cells compared to Neanderthal DNA. Kelso of the Max Planck Institute for Evolutionary Anthropology says the finding is consistent with other studies that have also linked Denisovan’s DNA to the immune system in Pacific Islanders.

So which immune genes exactly does Denisovan’s DNA turn on and off? It’s still a bit unknown, says Gallego Romero. This is because a non-coding sequence is not necessarily next to the gene it regulates and there could be more than one gene involved, especially if they are closely related to each other. Although there is a way to understand this with advanced genomic tools, such data is not yet available for every cell type.

The researchers were able to come closest to an answer by examining the activity of five specific Denisovan sequences in modified immune cell lines from a Papuan human donor. Within these cells, the sequences did different things, increasing or decreasing the activity of the immune genes they were also closest to, in ways that may impact how an individual responds to an infection. .

Why is it important – This study and others like it flesh out this murky picture of how some of our other long-dead prehistoric ancestors influenced our own evolution and health today. Gallego Romero says Denisovan’s DNA likely conferred a survival advantage, allowing indigenous peoples of the region to adapt and cope with new environmental pathogens as our ancestors moved out of Africa. According to some studies, this Denisovan DNA may still confer an immunological advantage today.

Apart from that, Gallego Romero claims that this study and similar research efforts expand the diversity of data, which is currently lacking.

“The human genetic datasets that have been used to understand Neanderthal DNA or to link it to phenotypes are mostly from people of European ancestry…and not really anyone else,” says -she. “Denisovan’s DNA is missing from [genomic datasets]it is missing from the UK Biobank, where you would go to determine what a [gene] Is.”

And after – Gallego Romero and his team plan to learn more about the impact of Denisovan DNA on our contemporary genomes and hope to work more closely with researchers in Indonesia and Papa New Guinea who would benefit immensely from this information.

“This work connects the past and present of our species in a way that is obvious to people, but I think, again, [makes] the past more knowable and tangible,” she says. “By looking at these genomes, we can understand a lot of things [were] the dynamics of these [ancient] the people and what they were doing.

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