Our species has a well-established history of interbreeding with other, now-extinct human groups, and those encounters still echo in our DNA today. A fresh analysis suggests that one particular genetic variant inherited from the Denisovans may have helped modern humans (Homo sapiens) succeed as they spread across the American continents.
"Typically, genetic novelty is generated through a very slow process," says evolutionary biologist Emilia Huerta-Sánchez, from Brown University in the US. "But these interbreeding events were a sudden way to introduce a lot of new variation."
How the Denisovans’ MUC19 variant reached Indigenous American genomes
The MUC19 region of the human genome encodes a mucin protein – which, as the name implies, plays a part in producing mucus, the gel-like material our cells secrete to build and lubricate the body.
Everyone carries MUC19 genes, yet people with Indigenous American ancestry are, compared with other populations, more likely to have a specific variant of this gene that can be traced back to the ancient (and now extinct) Denisovans.
By closely examining genetic data from both ancient remains and present-day people, Huerta-Sánchez and colleagues concluded that this variant did not enter our DNA via a single, straightforward handover. Instead, it followed a winding route that helped it persist long after the human group it came from had disappeared.
"Our results point to a complex pattern of multiple introgression events, from Denisovans to Neanderthals and Neanderthals to modern humans, which may have later played a distinct role in the evolutionary history of Indigenous American populations," the authors write.
That proposed pathway also helps clarify how a gene linked to an ancient human group known to have lived in Tibet and Siberia ended up in such a far-flung region, even though the Denisovans themselves do not appear to have reached the Americas.
Where the Denisovan DNA shows up most often
The Denisovan segment of DNA appeared at its highest frequencies in the genomes of 23 ancient Indigenous American individuals discovered at archaeological sites in Alaska, California, and Mexico. These remains date to before Europeans and Africans arrived on the continent.
Drawing on data from the 1,000 Genomes Project, a global survey of human genetic variation, the researchers also found that present-day Latino Indigenous Americans carry this Denisovan genetic signature at high frequencies.
What changed as Homo sapiens moved into North America
Using a suite of statistical tests, the team further showed that as Homo sapiens migrated into North America, they underwent a major expansion of repeated sequences within the MUC19 region of their genomes.
According to the authors, this expansion "effectively doubles the functional domain of this mucin, indicating an adaptive role driven by environmental pressures particular to the Americas."
The repetition occurred in a part of the gene that shapes the protein’s ability to bind sugars, enabling a stickier form of the mucin glycoprotein to form.
The researchers argue that producing stickier mucus must have delivered some advantage that boosted survival and reproduction in these unfamiliar environments.
Why stickier mucus might matter
Exactly what that advantage was is difficult to specify, but the authors point out that other mucin genes, such as MUC7, have variants with differing microbe-binding behaviour. Those differences can be vital for host–microbe symbiosis, including the kinds of relationships that take place in our guts, mouths, and nether regions.
It is possible that Denisovan-like genes helped humans collaborate with a beneficial North American microbe, or alternatively made it easier to exclude harmful ones.
"Something about this gene was clearly useful for these populations – and maybe still is or will be in the future," Huerta-Sánchez says. "We hope that leads to additional study of what this gene is actually doing."
This research is published in Science.
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