Thousands of years ago, long before the rise of civilizations, groups of ancient humans embarked on one of the most remarkable migrations in human history. They journeyed across the frozen expanse of the Bering Strait—a treacherous bridge of ice connecting Asia and North America—venturing into a world that no human had ever seen before. These early travelers, the ancestors of today’s Indigenous Americans, faced unimaginable challenges: new climates, new diseases, and unfamiliar ecosystems. Yet, as a recent study led by the University of Colorado Boulder reveals, they may have carried with them not just courage and resourcefulness, but also a hidden biological inheritance that would aid their survival—a piece of DNA from an extinct species of ancient human known as the Denisovans.
Published in the journal Science, the study provides groundbreaking insights into how genetic material from archaic hominins has influenced human adaptation. Co-led by anthropologist Fernando Villanea of the University of Colorado Boulder and David Peede of Brown University, the research suggests that a gene called MUC19, inherited from Denisovans through a complex chain of interbreeding, may have given early Americans a biological edge in surviving the harsh and diverse environments of the New World.
Unraveling the Mystery of the Denisovans
The Denisovans were a mysterious group of archaic humans who lived tens of thousands of years ago. Their fossils, first discovered in Siberia’s Denisova Cave just 15 years ago, have provided scientists with crucial DNA evidence but little understanding of what they looked like or how they lived. They likely ranged widely—from the icy expanses of Russia to the tropical islands of Oceania and the high-altitude regions of the Tibetan Plateau. Though now extinct, the Denisovans left a lasting mark on the genetic makeup of modern humans, particularly in Asia and the Pacific.
“We know more about their genomes and how their body chemistry behaves than we do about what they looked like,” Villanea remarked. This statement highlights a fascinating irony: despite their extinction, Denisovans continue to shape the biology of modern humans through the traces of DNA they left behind.
It is now well established that interbreeding between modern humans, Neanderthals, and Denisovans occurred multiple times throughout prehistory. As a result, most people today carry some genetic material from these ancient relatives—typically about 1–2% Neanderthal DNA in non-African populations, and up to 5% Denisovan DNA in people from Papua New Guinea. These ancient gene transfers, or “introgressions,” have influenced traits ranging from immune responses to high-altitude adaptation.
The Curious Case of the MUC19 Gene
In this study, Villanea and his team focused on MUC19, a gene associated with the production of mucins—proteins that create mucus and protect tissues from pathogens. While mucus may seem mundane, it plays a crucial role in immune defense, helping the body trap and eliminate harmful microbes. However, as Villanea pointed out, MUC19 remains poorly understood: “It seems like MUC19 has a lot of functional consequences for health, but we're only starting to understand these genes.”
Earlier studies revealed that Denisovans carried a distinct version of MUC19, marked by unique mutations not found in modern humans. This genetic variant was later passed on to humans through interbreeding, a process that allowed ancient populations to inherit potentially beneficial traits that improved their chances of survival.
To explore this further, the research team analyzed existing genomic data from populations across the Americas, including Mexico, Peru, Puerto Rico, and Colombia—regions with strong Indigenous American ancestry. Their findings were striking: about one in three people of Mexican ancestry carry a copy of the Denisovan variant of MUC19, particularly in parts of their genome linked to Indigenous heritage. In contrast, this variant is exceedingly rare among people of Central European descent, appearing in only about 1% of individuals.
An “Oreo” of Ancient DNA
The researchers uncovered something even more intriguing. The Denisovan MUC19 gene variant found in humans appeared to be “sandwiched” between stretches of DNA inherited from Neanderthals. Villanea playfully described it as “an Oreo, with a Denisovan center and Neanderthal cookies.”
This finding suggests a complex genetic history. Before modern humans migrated into the Americas, Denisovans and Neanderthals interbred, exchanging genetic material. Later, Neanderthals passed some of this Denisovan DNA to early modern humans during subsequent interbreeding events in Eurasia. This marks the first known instance of DNA passing from Denisovans to Neanderthals, and then to humans—a three-step transfer across species lines that reveals how interconnected the evolutionary web truly was.
Adapting to a New World
After this remarkable chain of genetic inheritance, the early humans who crossed the Bering Strait brought the Denisovan-derived MUC19 gene with them into the Americas. Once there, natural selection likely favored individuals carrying this variant, allowing it to become more common among Indigenous American populations.
Why did this happen? The researchers propose that as humans entered the Americas—an entirely new and ecologically diverse continent—they encountered novel challenges. These included unfamiliar diseases, different food sources, and extreme environmental conditions ranging from icy tundras to tropical forests. The Denisovan variant of MUC19 may have provided enhanced immune protection or other physiological advantages that helped early populations survive and thrive.
“All of a sudden, people had to find new ways to hunt, new ways to farm, and they developed really cool technology in response to those challenges,” Villanea noted. “But, over 20,000 years, their bodies were also adapting at a biological level.”
This dual adaptation—technological and biological—underscores the resilience of the first Americans. They not only invented tools and strategies suited to their new environments but also underwent genetic evolution shaped by the legacy of their ancient ancestors.
The Ongoing Quest to Understand Human Evolution
The discovery of the Denisovan MUC19 gene in Indigenous American populations adds another piece to the intricate puzzle of human evolution. It demonstrates how ancient DNA continues to influence modern human biology, often in ways that we are only beginning to grasp. Villanea and his team now plan to investigate how different variants of MUC19 affect human health today. Such studies could provide valuable insights into immune system function and disease resistance across populations.
The collaboration involved researchers from multiple prestigious institutions, including Brown University, the University of Washington School of Medicine, Universidad Nacional Autónoma de México, the University of Copenhagen, Clemson University, the University of Padova, the University of Turin, the University of California Berkeley, Université Paris-Saclay, and Trinity College Dublin. This global effort highlights the interdisciplinary and international nature of modern genetic research.
A Testament to Human Resilience
In the end, the study paints a powerful picture of human adaptability. The early settlers of the Americas not only crossed immense physical barriers but also carried within their DNA the evolutionary tools to survive in a new world. As Villanea eloquently put it, “What Indigenous American populations did was really incredible. They went from a common ancestor living around the Bering Strait to adapting biologically and culturally to this new continent that has every single type of biome in the world.”
This discovery also serves as a reminder that evolution is not a linear process but a complex tapestry woven from countless interactions, migrations, and exchanges of genetic material. The Denisovan DNA that once belonged to a long-extinct species continues to live on, quietly shaping the biology of millions of people today.
The story of the Denisovan MUC19 gene is more than just a tale of genetics—it’s a story of endurance, adaptation, and interconnectedness. It reveals how ancient interbreeding events, once seen as mere historical curiosities, played an essential role in the survival of our species. The early humans who ventured into the Americas carried with them not only their hopes and ingenuity but also the silent legacy of ancestors they never knew—ancestors whose DNA still whispers through the cells of their descendants, reminding us that the past is always present within us.
Story Source: University of Colorado at Boulder.
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