Genetic analysis shows leprosy was endemic in pre-colonial America

Long considered a disease brought to the Americas by European colonizers, leprosy may actually have a much older history on the American continent. Scientists from the Institut Pasteur, the CNRS, and the University of Colorado (USA), in collaboration with various institutions in America and Europe, reveal that a recently identified second species of bacteria responsible for leprosy, Mycobacterium lepromatosis, has been infecting humans in the Americas for at least 1,000 years, several centuries before the Europeans arrived. These findings will be published in the journal Science on May 29, 2025.

Leprosy is a neglected disease, mainly caused by the bacterium Mycobacterium leprae, affecting thousands of people worldwide: approximately 200,000 new cases of leprosy are reported each year. Although M. leprae remains the primary cause, this study focused on another species, Mycobacterium lepromatosis, discovered in the United States in 2008 in a Mexican patient, and later in 2016 in red squirrels in the British Isles. Led by scientists from the Laboratory of Microbial Paleogenomics at the Institut Pasteur, also associated with the CNRS, and the University of Colorado, in collaboration with Indigenous communities and over 40 scientists from international institutions including archaeologists, this study analyzed DNA from nearly 800 samples, including ancient human remains (from archaeological excavations) and recent clinical cases presenting symptoms of leprosy. The results confirm that M. lepromatosis was already widespread in North and South America long before European colonization and provide insights into the current genetic diversity of pathogenic Mycobacteria.

"This discovery transforms our understanding of the history of leprosy in America," said Dr. Maria Lopopolo, the first author of the study and researcher at the Laboratory of Microbial Paleogenomics at the Institut Pasteur. "It shows that a form of the disease was already endemic among Indigenous populations well before the Europeans arrived."

The team used advanced genetic techniques to reconstruct the genomes of M. lepromatosis from ancient individuals found in Canada and Argentina. Despite the geographic distance of several thousand kilometers, these ancient strains dating from similar periods (approximately 1,000 years ago) were found to be surprisingly genetically close. Although they belong to two distinct branches in the evolutionary tree of the genus Mycobacterium, these branches are genetically closer to each other than to any other known branch. This genetic proximity, combined with their geographical distance, necessarily implies a rapid spread of the pathogen across the continent, likely within just a few centuries.

The scientists also identified several new lineages, including an ancestral branch that despite having diverged from the rest of the known species' diversity over 9,000 years ago, it continues to infect humans today in North America - a discovery suggesting an ancient and long-lasting diversification on the continent, as well as a largely unexplored diversity that likely remains to be found.

Notably, the analyses also suggest that the strains found in red squirrels in the UK in 2016 are part of an American lineage that was introduced to the British Isles in the 19th century, where it subsequently spread. This discovery highlights the recent ability of the pathogen to cross continents, likely through human or commercial exchanges.

We are just beginning to uncover the diversity and global movements of this recently identified pathogen. The study allows us to hypothesize that there might be unknown animal reservoirs. This study clearly illustrates how ancient and modern DNA can rewrite the history of a human pathogen and help us better understand the epidemiology of contemporary infectious diseases."

Nicolás Rascovan, lead author of the study and head of the Laboratory of Microbial Paleogenomics at the Institut Pasteur

The project was conducted in close collaboration with Indigenous communities, which were involved in decisions regarding the use of ancestral remains and the interpretation of results. Ancient DNA and remaining materials were returned when requested, and the generated data was shared via ethical and adaptable platforms designed to allow data sharing that meets the specific expectations of Indigenous communities.