We often tell ourselves a comforting story about the history of disease: it’s the price of civilization. For most of human existence, we were healthy, free-roaming hunter-gatherers. It was only when we settled down, built cities, and started farming that the great plagues began.
But a 5,500-year-old skeleton from the Colombian highlands just shattered that narrative.
Inside the shin bone of a hunter-gatherer, scientists have recovered the DNA of Treponema pallidum—the bacterial family responsible for syphilis. The discovery reveals that these pathogens were stalking humanity in the Americas long before the rise of agriculture or urban life.
“Our results push back the association of T. pallidum with humans by thousands of years, possibly more than 10,000 years ago in the Late Pleistocene,” said researcher Davide Bozzi at the University of Lausanne and SIB Swiss Institute of Bioinformatics.
The discovery upends our timeline of infectious disease in the Americas, suggesting that the family of bacteria plaguing humanity today has been with us since the very first people crossed into the New World, sometime around 15,000 years ago.
The Invisible Passenger
Paleopathologists have typically relied on bones to tell the history of this dreadful disease. Syphilis and yaws leave gruesome signatures on the skeleton—”saber shins” or “caries sicca” they’re called—but only in advanced stages. However, this reliance on visible lesions has created a massive blind spot.
The team didn’t originally set out to find a pathogen. They were generating a staggering 1.5 billion fragments of genetic data to reconstruct human population history in the area. But when they screened that data, they found the distinct spiral-shaped bacteria lurking in the background.
“Our findings show the unique potential of paleogenomics to contribute to our understanding of the evolution of species, and potential health risks for past and present communities,” said geneticist Lars Fehren-Schmitz at the University of California, Santa Cruz.
The fact that this pathogen was found in a tibia without visible lesions is a game-changer. It implies that ancient DNA can reveal the “invisible” history of diseases that leave no trace on the bone, proving that “even bones without visible signs of disease could be valuable sources of pathogen DNA.”
A New Branch on the Family Tree
This wasn’t just an old case of syphilis. When the researchers reconstructed the genome, they found it didn’t match any known modern subspecies.
It wasn’t syphilis (T. pallidum subsp. pallidum), yaws (pertenue), or bejel (endemicum). It was a sister lineage to all of them—a long-lost relative that diverged from the family tree roughly 13,700 years ago.
“Our results provide a first look into the earlier stages of Treponema pallidum evolution,” Davide Bozzi told ZME Science. “With a genome 3000 years older than anything previously studied, we have been able to push the emergence of this pathogen several millennia back in time.”
“Additionally, we have revealed an entirely new subspecies that has never been observed before, greatly expanding the known diversity of human-associated T. pallidum lineages”.
This date—13,700 years ago—aligns with the time humans were first migrating into the Americas. When asked if the pathogen hitched a ride with the first Americans, Bozzi was cautious but intrigued.
“These results place the split within a time window that coincides with the first colonization of the American continent by human populations,” Bozzi said. “This could hint to a scenario where the first inhabitants of the American continent were exposed to a source of Treponema pallidum infection, such as a wild animal reservoir.”
“Yet, at present, the possibility that T. pallidum was already associated with the first human settlers cannot be fully excluded. Future research that extends into the study of animal infections from faunal remains and/or more genomic data from millenia-old populations could help us untangle this riddle concerning the initial emergence of T. pallidum as a human pathogen.”
The Pinta Puzzle
The discovery also casts light on a “dark matter” problem in the world of treponemal diseases: pinta.
Pinta is a mild skin disease caused by Treponema carateum, found in Central and South America. Unlike its cousins, pinta has never been sequenced, so its place on the evolutionary tree is a mystery.
Could this 5,500-year-old bacteria be an ancient ancestor of pinta?
“One possibility is that we uncovered an ancient form of the pathogen that causes pinta, which we know little about, but is known to be endemic in Central to South America and causes symptoms localized to the skin,” said Anna-Sapfo Malaspinas at the University of Lausanne.
Bozzi expanded on this hypothesis: “An alternative scenario could imply this strain to be an ancestral form of the causative agent of pinta, a neglected tropical disease endemic to Central and South America and for which we have no modern genomic data. Future research on this disease and the genomic characterization of its pathogen will be essential to understand which of the two scenarios is the correct one.”
Reframing the “Columbian Theory”
Few diseases carry as much historical baggage as syphilis. For centuries, the “Columbian Hypothesis” has argued that Columbus and his crew brought the sexually transmitted plague back to Europe from the Americas in 1492.
While this new genome doesn’t definitively solve that geopolitical blame game, it drastically changes the context. We now know that diverse, virulent treponemal pathogens were circulating in the Americas thousands of years before European ships appeared on the horizon.
“Current genomic evidence, along with our genome presented here, does not resolve the long-standing debate about where the disease syndromes themselves originated, but it does show there’s this long evolutionary history of treponemal pathogens that was already diversifying in the Americas thousands of years earlier than previously known,” said Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU.
The narrative is shifting from “who gave it to whom” to a story of deep, global evolutionary history.
“Paleogenomic evidence is now pointing towards an ancient diversification of Treponema pallidum subspecies within the American continent several millennia ago, with a subsequent spread to other regions of the globe during colonial times. That said, when exactly in human history the different present-day diseases emerged remains an open question,” Bozzi told ZME Science.
Diseases of the Hunter-Gatherers
Perhaps most surprisingly, this research challenges the idea that sophisticated diseases require sophisticated civilizations.
This individual was a hunter-gatherer living in the Middle Holocene. The pathogen’s emergence wasn’t driven by agricultural intensification or population density. Instead, it thrived in the social and ecological conditions of mobile groups.
The genome analysis showed that this ancient strain was no weakling either; it carried the “full suite of genetic features associated with virulence in modern T. pallidum,” the researchers write. This suggests that sophisticated, virulent pathogens have been shaping human biology long before we laid the first brick of the first city.
Getting to these conclusions wasn’t easy. The DNA was old, fragmented, and sort of weird. Because the genome was so different from modern references, the team had to use advanced simulations to confirm what they were seeing.
“The extremely divergent nature of this genome forced us to conduct extensive phylogenetic analyses to confirm its ‘phylogenetic placement’,” Bozzi said. “By employing different methodologies, as well as simulations, we were able to show that different approaches lead to the same conclusion: this ancient genome represents an early-diverging subspecies of T. pallidum”.
The study also sets a new standard for ethical paleogenomics. The researchers engaged deeply with Colombian communities, ensuring the findings were communicated with respect for the country’s medical and cultural history.
“This process was essential because the findings are deeply connected to Colombia’s medical and cultural history,” said archaeologist Miguel Delgado. “Engaging scholars, students, and Indigenous and non-Indigenous community members ensures the results are ethically communicated and interpreted in partnership with local communities”.
The new findings appeared in the journal Science.
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