Extinct human relatives left a genetic gift that helped people thrive in the Americas
A new study found that a gene passed down from extinct archaic humans provided an adaptive advantage for Indigenous people of the Americas and is still common today in people of Indigenous descent
Brown University
PROVIDENCE, R.I. [Brown University] — A new study provides fresh evidence that ancient interbreeding with archaic human species may have provided modern humans with genetic variation that helped them adapt to new environments as they dispersed across the globe.
The study, published in Science, focused on a gene known as MUC19, which is involved in the production of proteins that form saliva and mucosal barriers in the respiratory and digestive tracts. The researchers show that a variant of that gene derived from Denisovans, an enigmatic species of archaic humans, is present in modern Latin Americans with Indigenous American ancestry, as well as in DNA collected from individuals excavated at archeological sites across North and South America.
The frequency at which the gene appears in modern human populations suggests the gene was under significant natural selection, meaning it provided a survival or reproductive advantage to those who carried it. It’s not clear exactly what that advantage might have been, but given the gene’s involvement in immune processes, it may have helped populations to fight off pathogens encountered as they migrated into the Americas thousands of years ago.
“From an evolutionary standpoint, this finding shows how ancient interbreeding can have effects that we still see today,” said study author Emilia Huerta-Sánchez, a professor of ecology, evolution and organismal biology at Brown University. “From a biological standpoint, we identify a gene that appears to be adaptive, but whose function hasn’t yet been characterized. We hope that leads to additional study of what this gene is actually doing.”
Huerta-Sanchez co-authored the study with Fernando Villanea, a former post-doctoral researcher at Brown who is now at University of Colorado, Boulder; David Peede, a graduate student at Brown; and an international team of collaborators.
Not much is known about the Denisovans, who lived in Asia between 300,000 and 30,000 years ago, aside from a few small fossils from Denisova cave in Siberia, two jaw bones found in Tibet and Taiwan, and a nearly complete skull from China found this year. The finger fossil from Siberia contained ancient DNA, which enables scientists to look for common genes between Denisovans and modern humans. Prior research led by Huerta-Sánchez found that a version of a gene called EPAS1 acquired from Denisovans may have helped Sherpas and other Tibetans to adapt to high altitudes.
For this study, the researchers compared Denisovan DNA with modern genomes collected through the 1,000 Genomes Project, a survey of worldwide genetic variation. The researchers found that the Denisovan-derived MUC19 gene is present in high frequencies in Latino populations who harbor Indigenous American genetic ancestry. The researchers also looked for the gene in the DNA of 23 individuals collected from archeological sites in Alaska, California, Mexico and elsewhere in the Americas. The Denisovan-derived variant was present at high frequency in these ancient individuals as well.
The team used several independent statistical tests to show that the Denisovan MUC19 gene variant rose to unusually high frequencies in ancient Indigenous American populations and present-day people of Indigenous descent, and that the gene sits on an unusually long stretch of archaic DNA — both signs that natural selection had boosted its prevalence. The research also revealed that the gene was likely passed through interbreeding from Denisovans to another archaic population, the Neanderthals, who then interbred with modern humans.
Huerta-Sánchez said the findings demonstrate the importance that interbreeding had in introducing new and potentially useful genetic variation in the human lineage.
“Typically, genetic novelty is generated through a very slow process,” Huerta- Sánchez said. “But these interbreeding events were a sudden way to introduce a lot of new variation.”
In this case, she said, that “new reservoir of genetic variation” appears to have helped modern humans as they migrated into the Americas, perhaps providing a boost to the immune system.
“Something about this gene was clearly useful for these populations — and maybe still is or will be in the future,” Huerta-Sánchez said.
She’s hopeful that the recognition of the gene’s importance will spur new research into its function to reveal novel biological mechanisms, especially since it involves coding genetic variants that alter the protein sequence.
The research was supported by The Leakey Foundation, the National Institutes of Health (1R35GM128946- 01, T32 GM128596, R35GM142978, R01NS122766), the Alfred P. Sloan Foundation, the Blavatnik Family Graduate Fellowship in Biology and Medicine, the Brown University Predoctoral Training Program in Biological Data Science (NIH T32 GM128596), the Burroughs Wellcome Fund and the Human Frontier Science Program.
Journal
Science
Method of Research
Experimental study
Subject of Research
People
Article Title
The MUC19 gene: An Evolutionary History of Recurrent Introgression and Natural Selection
Article Publication Date
21-Aug-2025
DNA from extinct hominin may have helped ancient peoples survive in the Americas
Thousands of years ago, ancient humans undertook a treacherous journey, crossing hundreds of miles of ice over the Bering Strait to the unknown world of the Americas.
Now, a new study led by the University of Colorado Boulder suggests that these nomads carried something surprising with them—a chunk of DNA inherited from a now-extinct species of hominin, which may have helped humans adapt to the challenges of their new home.
The researchers will publish their results Aug. 21 in the journal Science.
“In terms of evolution, this is an incredible leap,” said Fernando Villanea, one of two lead authors of the study and an assistant professor in the Department of Anthropology at CU Boulder. “It shows an amount of adaptation and resilience within a population that is simply amazing.”
The research takes a new look at a species known as Denisovans. These ancient relatives of humans lived from what is today Russia south to Oceania and west to the Tibetan Plateau. The Denisovans likely went extinct tens of thousands of years ago. Their existence, however, remains poorly understood: Scientists identified the first known Denisovan just 15 years ago from the DNA in a fragment of bone found in a cave in Siberia. Like Neanderthals, Denisovans may have had prominent brows and no chins.
“We know more about their genomes and how their body chemistry behaves than we do about what they looked like,” Villanea said.
A growing body of research has shown that Denisovans interbred with both Neanderthals and humans, profoundly shaping the biology of people living today.
To explore those connections, Villanea and his colleagues including co-lead author David Peede from Brown University, examined the genomes of humans from across the globe. In particular, the team set its sights on a gene called MUC19, which plays an important role in the immune system.
The group discovered that humans with Indigenous American ancestry are more likely than other populations to carry a variant of this gene that came from Denisovans. In other words, this ancient genetic heritage may have helped humans survive in the completely new ecosystems of North and South America.
A little-known gene
Villanea added that MUC19’s function in the human body is about as mysterious as Denisovans themselves. It’s one of 22 genes in mammals that produce mucins. These proteins make mucus, which, among other functions, can protect tissues from pathogens.
“It seems like MUC19 has a lot of functional consequences for health, but we’re only starting to understand these genes,” he said.
Previous research has shown that Denisovans carried their own variant of the MUC19 gene, with a unique series of mutations, which they passed onto some humans. That kind of admixture was common in the ancient world: Most humans alive today carry some Neanderthal DNA, whereas Denisovan DNA makes up as much as 5% of the genomes of people from Papua New Guinea.
In the current study, Villanea and colleagues wanted to learn more about how these genetic time capsules shape our evolution.
The group pored through already published data on the genomes of modern humans from Mexico, Peru, Puerto Rico and Colombia where Indigenous American ancestry and DNA is common.
They discovered that one in three modern people of Mexican ancestry carry a copy of the Denisovan variant of MUC19—and particularly in portions of their genome that come from Indigenous American heritage. That’s in contrast to people of Central European ancestry, only 1% of whom carry this variant.
The researchers discovered something even more surprising: In humans, the Denisovan gene variant seems to be surrounded by DNA from Neanderthals.
“This DNA is like an Oreo, with a Denisovan center and Neanderthal cookies,” Villanea said.
A new world
Here’s what Villanea and his colleagues suspect happened: Before humans crossed the Bering Strait, Denisovans interbred with Neanderthals, passing the Denisovan MUC19 to their offspring. Then, in a game of genetic telephone, Neanderthals bred with humans, sharing some Denisovan DNA. It’s the first time scientists have identified of DNA jumping from Denisovans to Neanderthals and then humans.
Later, humans migrated to the Americas where natural selection favored the spread of this borrowed MUC19.
Why the Denisovan variant became so common in North and South America but not in other parts of the world isn’t yet clear. Villanea noted that the first people who lived in the Americas likely encountered conditions unlike anything else in human history, including new kinds of food and diseases. Denisovan DNA may have given them additional tools to contend with challenges like these.
“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,” he said. “But, over 20,000 years, their bodies were also adapting at a biological level.”
To build that picture, the anthropologist is planning to study how different MUC19 gene variants affect the health of humans living today. For now, Villanea said the study is a testament to the power of human evolution.
“What Indigenous American populations did was really incredible,” Villanea said. “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.”
Other co-authors of the new study include researchers at Brown University; the University of Washington School of Medicine; Universidad Nacional Autónoma de México; University of Copenhagen; Clemson University; University of Padova; University of Turin; University of California, Berkeley; Université Paris- Saclay; and Trinity College Dublin.
Journal
Science
Article Title
The MUC19 gene: An evolutionary history of recurrent introgression and natural selection
Article Publication Date
21-Aug-2025
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