New research has revealed that an extinct group of ancient humans called Denisovans passed down a crucial genetic inheritance that continues to benefit Indigenous American populations today. The study, published in Science, demonstrates how a specific gene variant acquired through ancient interbreeding provided survival advantages to the first peoples of the Americas and remains prevalent in modern populations with Native American ancestry.
The discovery centers on a gene known as MUC19, which plays a vital role in producing proteins that form protective barriers in the respiratory and digestive systems. This Denisovan-derived variant appears to have been under strong natural selection, meaning it provided significant survival benefits to those who carried it during the challenging migration into the Americas thousands of years ago.
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The figure depicts the deep ancestries of the ancient individuals of the Americas and archaic ancestry in ancient South America and Panama. The pie chart radius reflects the proportion of shared archaic ancestry in the individual. (Florida Atlantic University)
The Mysterious Denisovans: Asia's Ghost Population
The Denisovans remain one of paleontology's most enigmatic puzzles. These archaic humans lived across Asia between 300,000 and 30,000 years ago, yet scientists know them primarily through genetic analysis rather than fossil evidence. Only a handful of physical remains have been discovered: fragmentary bones from Denisova Cave in Siberia, two jaw bones found in Tibet and Taiwan, and a nearly complete skull from China found this year.
Despite their scant fossil record, Denisovans have left an indelible mark on the human genome. Previous research led by Dr. Emilia Huerta-Sánchez from Brown University identified that a version of the EPAS1 gene, also inherited from Denisovans, helps modern Tibetan populations adapt to high-altitude environments.
Holotype cranium of Homo longi, identified as the same species as Denisovan. (Fu et al. (2025)/ CC BY 4.0)
Ancient DNA Reveals Survival Advantages
The research team compared Denisovan DNA with modern genomes from the 1,000 Genomes Project, revealing that the Denisovan-derived MUC19 gene variant occurs at remarkably high frequencies in Latino populations carrying Indigenous American genetic ancestry. To verify their findings across time, researchers examined DNA from 23 individuals recovered from archaeological sites spanning Alaska, California, Mexico, and other locations throughout the Americas.
Remarkably, the Denisovan-derived gene variant appeared at high frequencies in these ancient individuals as well, some dating back thousands of years. The gene sits on an unusually long stretch of archaic DNA, clear indicators that natural selection had actively favored its preservation and spread.
The study revealed the complex pathway through which this beneficial gene reached modern humans. The Denisovan variant was likely first passed through interbreeding to Neanderthals, who then interbred with modern humans. This multi-step genetic transfer highlights the interconnected nature of ancient human populations.
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Genetic Protection for New World Pioneers
The MUC19 gene's specific function involves producing mucins - glycoproteins that form protective gels in various body systems. These proteins play crucial roles in immune defense, particularly in the respiratory and digestive tracts where they help protect against pathogens and environmental threats.
Given the gene's involvement in immune processes, researchers believe the Denisovan variant may have provided enhanced protection against diseases encountered during the challenging migration into the Americas. The first peoples to cross into the New World faced entirely new environments, climates, and potentially novel pathogens, making any genetic advantage in immune function potentially life-saving.
"From an evolutionary standpoint, this finding shows how ancient interbreeding can have effects that we still see today," explained Dr. Huerta-Sánchez. "Something about this gene was clearly useful for these populations — and maybe still is or will be in the future."
The Cygnus Key: A Chance to Meet the Denisovans Webinar, from the AO Store.
Modern Implications and Future Research
The Denisovan MUC19 variant remains common in contemporary populations with Indigenous American ancestry, including many Latino communities throughout North and South America. This genetic inheritance represents a tangible link between modern Indigenous peoples and their ancient ancestors, providing molecular evidence of the remarkable journey that brought the first humans to the Americas.
The discovery demonstrates how ancient interbreeding events served as crucial sources of genetic innovation. Rather than the slow process of random genetic mutation, these encounters provided "a sudden way to introduce a lot of new variation" that proved essential for human adaptation to new environments.
The recognition of MUC19's evolutionary importance is expected to stimulate new research into its specific biological mechanisms. Understanding how ancient genetic variants continue to influence modern human health could lead to new insights into immune system function and disease resistance, potentially informing medical research for generations to come.
Top image: AI impression of a Denisovan face. Source: Prompt World/Adobe Stock
By Gary Manners
References
Huerta-Sánchez, E. et al. 2024. Extinct human relatives left a genetic gift that helped people thrive in the Americas. Available at: https://www.brown.edu/news/
Villanea, F. et al. 2024. The MUC19 Gene: An Evolutionary History of Recurrent Introgression and Natural Selection. Available at: https://www.biorxiv.org/content/10.1101/2023.09.25.559202v2
Villanea, F. et al. 2024. The MUC19 gene: An evolutionary history of recurrent introgression and natural selection Available at: https://dx.doi.org/10.1126/science.adl0882
