In northern Chile, two men were buried nearly 4,000 years ago. Now, their well-preserved bones have revealed something unexpected: the genetic traces of Mycobacterium lepromatosis, one of the bacteria that causes Hansen’s disease, better known as leprosy.
The discovery was surprising since the bacterial infection known to cause severe, disfiguring skin sores and nerve damage in the limbs was always thought to have arrived in the Americas with European colonizers.
“We were initially suspicious, since leprosy is regarded as a colonial-era disease,” said Darío Ramirez, an anthropologist at the National University of Córdoba in Argentina and lead author of the study, in a press release. “But more careful evaluation of the DNA revealed the pathogen to be of the lepromatosis form.”
This finding suggests that M. lepromatosis may have been present in the Americas for thousands of years and followed a separate evolutionary path from its better-known relative, M. leprae.
Ancient Strain, Separate Path
The bones came from two adult males excavated from separate archaeological sites—El Cerrito and La Herradura—in the semi-arid coastal region near Coquimbo, Chile. Both skeletons bore subtle signs of leprosy-like illness: thickened leg bones, pitted hand bones, and reshaped nasal structures. These were not definitive evidence of leprosy on their own. But when Ramirez and his colleagues sampled a tibia and a tooth, they found something rare: fragments of ancient DNA that closely matched Mycobacterium lepromatosis.
The reconstruction identified the bacterium and revealed that it had diverged significantly from M. leprae, which spread across Eurasia during the Neolithic period. Unlike M. leprae, which has been extensively studied through archaeological samples and historical records, M. lepromatosis was first identified only in 2008. Scientists have associated it with some of the most severe forms of Hansen’s disease, including diffuse lepromatous leprosy and the potentially fatal Lucio’s phenomenon (a severe, necrotizing skin reaction associated with diffuse lepromatous leprosy, a rare form of leprosy).
The genomic differences between the two species are stark. A pangenome analysis showed that only about half of the protein-coding genes shared 50% or greater similarity between M. leprae and M. lepromatosis. At the nucleotide level, they share just 25% identity—a pretty big split for two pathogens that cause the same disease.
What the Bones Reveal
Radiocarbon dating placed both individuals at around 3,900 to 4,100 years ago—centuries before the Olmec built pyramids and millennia before Columbus crossed the Atlantic. The researchers enriched the ancient DNA using a capture method designed for M. leprae but still managed to pull out two high-coverage M. lepromatosis genomes.
The team then built a time-calibrated phylogenetic tree that included both ancient and modern M. lepromatosis strains. They found the ancient genomes did not nest among the modern human strains. Instead, they formed a sister group—a lineage on its own branch.
“The median time for the most recent common ancestor of M. lepromatosis is estimated to be about 26,800 years ago,” the authors wrote. For the human-infecting strains, divergence appears to have begun around 12,600 years ago, well before the first complex societies in the Americas.
This suggests that M. lepromatosis may have either arrived with some of the earliest human migrations into the continent or evolved in an unknown animal reservoir already present in the region.
“Whether M. lepromatosis originated in the Americas or came with the first settlers from Eurasia remains to be determined,” said Kirsten Bos, senior author of the study and head of the Molecular Paleopathology group at the Max Planck Institute.
The Pre-Colonial Plagues We Missed
In historical accounts, the illness often appears alongside ships, slavery, and missionary hospitals. Researchers had believed that skeletal markers of leprosy were absent in pre-contact remains from the Americas, so not much effort has been expended in looking for such signs.
But the bones from Chile tell a different story.
“These ancient DNA findings are reshaping what we thought we knew,” Bos said. “The advanced techniques now used to study ancient pathogen DNA allow us to look beyond the suspects and into other diseases that might not be expected from the context.”
Researchers have previously identified M. lepromatosis in the Americas, with modern infections reported in Mexico and the Caribbean. In recent years, they also found DNA traces in human remains from Canada and Argentina dating back 1,000 years. But until now, they had not recovered a complete ancient genome—let alone one this old.
The findings underscore how much remains hidden in the Americas’ deep epidemiological past. Unlike in Eurasia, where people documented the history of infectious diseases extensively, communities in the pre-contact Americas left behind fewer written records. Later pandemics—especially smallpox, measles, and influenza—swept across the continent and obscured much of its earlier disease history.
“This disease was present in Chile as early as 4,000 years ago,” said Rodrigo Nores, a professor of anthropology at the University of Córdoba and co-author of the study. “Now that we know it was there, we can specifically look for it in other contexts.”
What Comes Next?
Today, Hansen’s disease is rare and curable. It still affects around 180,000 people globally, according to the World Health Organization. But the stigma surrounding leprosy remains strong, and in some regions, treatment can be difficult to access.
And there are new questions to answer. In Europe, red squirrels are known reservoirs for M. lepromatosis and M. leprae. In the Americas, armadillos carry M. leprae, but no animal has yet been found to host M. lepromatosis. The individuals in this study lived well outside the current range of armadillos. So the researchers wondered: could an unknown reservoir species have once harbored the pathogen?
The findings call for a broader “One Health” approach—linking human health with that of animals and the environment. “Greater awareness of this pathogen and its potential for zoonotic transmission… is needed,” the study notes.
The findings appeared in Nature Ecology & Evolution.
