Thousands of years ago, ancient Homo sapiens embarked on a perilous journey, traversing the icy expanses of the Bering Straits into the uncharted territories of the Americas. Recent research indicates that these migrants may have brought with them an extraordinary gift – MUC19 genes inherited from Denisovans, which could have played a pivotal role in helping humans adapt to the challenges of their new environments.

The modern human genome harbors a few archaic variants that are the remnants of past interbreeding events with Neanderthals and Denisovans.

While many of these variants are neutral, certain archaic mutations found in modern humans are believed to be targets of positive natural selection, possibly essential for human adaptation as they expanded into new lands.

The populations in the Americas encountered diverse environments, creating numerous opportunities for natural selection to favor archaic variations in these new settings.

This new research, spearheaded by a team from the University of Colorado, Boulder, and Brown University, focused on a gene known as MUC19, which aids in the production of proteins that form saliva and mucosal barriers in the respiratory and gastrointestinal tracts.

The researchers found that a Denisovan variant of MUC19 exists in the DNA of modern Latin Americans with Indigenous American ancestry, as well as in individuals excavated from archaeological sites across North and South America.

The prevalence of this gene in modern human populations suggests it was under significant natural selection, indicating that it conferred survival or reproductive advantages to those who carried it.

Although the specific benefits remain unclear, given the gene’s involvement in immune processes, it may have provided an enhanced defense against pathogens encountered by early settlers in the Americas.

“From an evolutionary perspective, this discovery illustrates how ancient interbreeding can produce effects that persist today,” stated Professor Emilia Fuerta Sanchez of Brown University.

“Biologically, it identifies genes that seem to be adaptable, though their precise functions are yet to be elucidated.”

“We hope this will spur further research into the actual roles of this gene.”

Limited information exists about Denisovans, who inhabited Asia between 300,000 and 30,000 years ago, with our knowledge primarily derived from small fossils found in Denisova Cave, two jawbones discovered in Tibet and Taiwan, and an almost complete skull unearthed in China this year.

Fossils from Siberian fingers contained ancient DNA, facilitating the search for genetic similarities between Denisovans and modern humans.

Previous studies have indicated that the Denisovan-derived gene EPAS1 may have contributed to the remarkable adaptations of Sherpas and other Tibetans.

In the current study, researchers compared Denisovan DNA with the most recent genomes obtained from the 1,000 Genomes Project, a global study on genetic variations.

They found that Denisovan-derived MUC19 variants are prevalent among Latino populations with Indigenous American ancestry.

The researchers also investigated DNA from 23 individuals excavated from archaeological sites in Alaska, California, Mexico, and other parts of the Americas, finding that Denisovan-derived variants were also common in these ancient peoples.

The authors conducted several independent statistical tests demonstrating that Denisovan MUC19 genetic mutations have reached unusually high frequencies in both ancient indigenous populations and present-day indigenous peoples, indicating genes that are situated on long stretches of archaic DNA.

They also revealed that the gene likely crossed over from Denisovans to another archaic population.

“These findings reveal that past interbreeding has introduced new and potentially advantageous genetic variations into human lineages,” Professor Fuerta Sanchez remarked.

“New genetic variations typically arise through slow evolutionary processes.”

“However, these interbreeding events were a sudden means of introducing a plethora of new variations.”

“In this instance, the novel genetic reservoir seems to have aided modern humans migrating to the Americas and may have bolstered their immune systems.”

“Clearly, this gene was advantageous for these populations.”

“We hope that recognizing the significance of these genes will inspire new investigations into their functions to uncover fresh biological mechanisms, particularly relating to coding genetic variants that modify protein sequences.”

Study published in the journal Science.

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Fernando A. Villania et al. 2025 MUC19 Genes: The evolutionary history of recurrent variants and natural selection. Science 389 (6762); doi:10.1126/science.adl0882