Ancient Genome of Treponema pallidum Reconstructed from 5,500-Year-Old Colombian Human Remains, Rewriting the History of Syphilis and Related Diseases

Scientists have successfully reconstructed the genome of Treponema pallidum, the bacterium responsible for syphilis and other serious infectious diseases, from human remains approximately 5,500 years old discovered in Colombia’s Sabana de Bogotá region. This groundbreaking finding, published in the prestigious journal Science, dramatically expands the known timeline of these infections in human populations, pushing back their genetic history by over three millennia and offering unprecedented insights into the evolution of ancient pathogens. The discovery challenges long-held assumptions about the origins and spread of treponemal diseases, particularly the enduring debate surrounding the "Columbian Exchange" hypothesis.

Unearthing an Ancient Pathogen in the Andes

The human remains, excavated from the Tequendama 1 rock shelter near present-day Bogotá, Colombia, represent a pivotal point in the archaeological record of the Americas. Radiocarbon dating places the individual’s life roughly 5,500 years ago, making this the oldest Treponema pallidum genome ever recovered. This archaeological site, renowned for its continuous human occupation spanning thousands of years, has provided invaluable data on early human settlements, subsistence strategies, and environmental adaptations in the Andean region. The discovery of an ancient pathogen within these remains underscores the site’s significance not only for human history but also for understanding the co-evolution of humans and their diseases. By identifying this remarkably preserved ancient genome, researchers have extended the known genetic history of Treponema pallidum by more than 3,000 years, providing compelling evidence that treponemal diseases circulated in the Americas far earlier than previously documented.

"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," stated geneticist Lars Fehren-Schmitz at the University of California, Santa Cruz, highlighting the transformative power of ancient DNA research. This research bridges the gap between traditional paleopathology, which relies on skeletal markers, and molecular biology, offering a much more precise and ancient view of disease dynamics.

The Enigmatic Family of Treponemal Diseases

Treponema pallidum is a spiral-shaped bacterium, or spirochete, known for its intricate relationship with human hosts. Today, it exists primarily in three closely related subspecies, each responsible for a distinct disease:

• Treponema pallidum subsp. pallidum: Causes syphilis, a sexually transmitted infection that can manifest in primary, secondary, latent, and tertiary stages, leading to severe systemic complications affecting the brain, heart, and other organs if left untreated. Historically, syphilis has caused immense suffering and societal disruption worldwide.
• Treponema pallidum subsp. pertenue: Causes yaws, a chronic skin, bone, and joint infection primarily found in tropical and subtropical regions. It is transmitted through direct skin-to-skin contact, typically among children, and while not sexually transmitted, it can be disfiguring and debilitating.
• Treponema pallidum subsp. endemicum: Causes bejel (or endemic syphilis), a non-sexually transmitted treponemal infection found mainly in arid regions of Africa and the Middle East. Like yaws, it is spread through direct contact, often via shared eating utensils or close living conditions, and affects the skin, mucous membranes, and bones.

A fourth treponemal disease, pinta, caused by Treponema carateum or Treponema pallidum subsp. carateum, primarily affects the skin, causing characteristic depigmented patches. Unlike the other three, a complete genome of the pathogen responsible for pinta has not yet been recovered, leaving significant gaps in our understanding of its evolutionary relationships and classification. Despite their nearly identical genetic makeup—often sharing over 99.8% sequence identity—scientists still grapple with understanding when and how these different disease forms emerged and diversified. While skeletal remains can sometimes show signs of treponemal infection, such as characteristic bone lesions, genetic evidence often tells a far more complex and ancient story, pushing timelines back much further than skeletal pathology alone can suggest.

A Lost Lineage Rewrites Evolutionary History

The most profound revelation of this study is that the ancient DNA recovered belonged to the species Treponema pallidum, but it did not match any of the known forms that cause disease today. Although closely related to modern strains, the ancient genome represents a distinct lineage that diverged very early in the bacterium’s evolutionary history. This "lost lineage" suggests a much greater diversity of treponemal pathogens in the ancient past than previously understood.

"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," suggested Anna-Sapfo Malaspinas at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics. "At this time, we cannot prove this is the case, but it is a lead worth investigating further." The geographical context of the discovery, in the Americas where pinta is historically endemic, lends credence to this hypothesis.

Based on detailed genetic analysis, scientists estimate that this ancient Colombian strain separated from other T. pallidum lineages approximately 13,700 years ago. This divergence places its origins deep within the Late Pleistocene epoch, a period coinciding with the initial migrations of humans into the Americas. In stark contrast, the three modern subspecies (syphilis, yaws, bejel) appear to have diverged much later, around 6,000 years ago. These vastly different timelines not only support earlier research suggesting a long evolutionary history for treponemal pathogens but also highlight the extensive diversification that occurred thousands of years before the emergence of the disease forms we recognize today.

"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," explained Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU. This finding significantly contributes to the "Columbian Exchange" debate, a historical discussion centered on whether syphilis originated in the New World and was brought to Europe by Columbus’s crew, or vice versa for other treponemal infections. The presence of a highly divergent T. pallidum lineage in the Americas over 5,000 years ago strongly supports an ancient and diverse presence of these pathogens on the continent, predating European contact by millennia. It suggests that various forms of treponemal diseases may have co-evolved with indigenous American populations for extended periods.

Paleogenomics: A Genetic Puzzle with Modern Implications

Tracing the origins and evolutionary paths of treponemal diseases has always been especially challenging due to the bacteria’s extreme genetic similarity across subspecies, even as they spread through different modes of transmission and cause vastly different clinical symptoms. This genetic subtlety makes traditional epidemiological and paleopathological studies difficult, underscoring the necessity of high-resolution ancient DNA analysis.

"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," emphasized researcher Davide Bozzi at the University of Lausanne and SIB Swiss Institute of Bioinformatics. This deep temporal reach into human-pathogen co-evolution offers a unique perspective on the microbial landscape encountered by early human migrants as they populated the Americas. Understanding such ancient interactions can provide crucial context for how pathogens adapt, diversify, and jump between hosts over vast timescales.

The discovery itself was not intentionally sought at first. Researchers were initially sequencing the individual’s DNA to study ancient human population history in the Americas, generating an enormous dataset of approximately 1.5 billion fragments of genetic data—a volume far exceeding typical ancient DNA sequencing efforts. During routine bioinformatics screening, teams at the University of California, Santa Cruz, and the University of Lausanne independently detected faint but distinct traces of T. pallidum DNA. Recognizing the immense potential of this unexpected find, they decided to combine their efforts and investigate collaboratively.

Remarkably, although bacterial DNA constituted only a tiny fraction of the total genetic material, the sheer depth of sequencing allowed the team to reconstruct the pathogen’s nearly complete genome without employing specialized enrichment techniques. This achievement demonstrates the power of ultra-high-throughput sequencing in uncovering microbial "dark matter" within ancient human remains.

Furthermore, the pathogen was recovered from a tibia, or shin bone—a skeletal element not commonly prioritized for ancient DNA studies. Most previous ancient Treponema pallidum genomes have been recovered from teeth or bones that clearly showed macroscopic signs of disease. In this case, the skeleton showed no visible evidence of infection, challenging the assumption that only visibly diseased bones yield valuable pathogen DNA. The success of this approach suggests that even skeletal elements without obvious pathological markers can preserve invaluable genetic information, opening new avenues for future paleogenomic research and significantly expanding the pool of potential samples for studying ancient infections.

Ethical Science: Community Engagement in Colombia

Recognizing the profound cultural and medical significance of their findings, the research team adopted a rigorous ethical framework for their work. Before publishing the results, they proactively shared their findings with communities in Colombia. This involved extensive consultation with local scholars, students, and both Indigenous and non-Indigenous community members, engaging stakeholders through presentations, workshops, and interviews. All required permits for the export and study of the human remains were meticulously obtained, ensuring compliance with national and international regulations.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," highlighted Miguel Delgado, an archaeologist of the Universidad Nacional de La Plata in Argentina, who has long been involved with the Tequendama 1 site. "Engaging scholars, students, and Indigenous and non-Indigenous community members ensures the results are ethically communicated and interpreted in partnership with local communities. This approach builds trust, supports responsible stewardship of sensitive discoveries, and reinforces local ownership of knowledge." This commitment to community engagement sets a vital precedent for future paleogenomic research, emphasizing the importance of respecting cultural heritage and fostering collaborative relationships with the communities whose ancestors contribute to scientific understanding.

Broader Implications for Health and Archaeology

The implications of this discovery are far-reaching, impacting our understanding of both ancient disease and modern public health. By learning how infectious diseases emerged, diversified, and adapted in the past, scientists can gain critical insights into the fundamental mechanisms of pathogen evolution. This historical perspective can help anticipate how pathogens might evolve in the future, how they might respond to environmental changes, and how they might develop resistance to treatments. This knowledge is crucial for preparing modern societies for potential health threats, including the emergence of new strains or the re-emergence of old ones. For instance, understanding the ancient genetic diversity of T. pallidum could inform vaccine development strategies or shed light on why certain subspecies cause different disease manifestations despite their genetic similarity.

For archaeology and paleopathology, the success of recovering a pathogen genome from an undiseased bone, particularly a tibia, expands the methodological toolkit for ancient DNA studies. It suggests that a broader range of human remains could harbor valuable genetic information about ancient diseases, even in the absence of macroscopic skeletal lesions. This opens up new possibilities for reconstructing the disease landscape of past populations, enabling a more comprehensive understanding of health, migration, and human-pathogen interactions throughout history.

An International Collaborative Endeavor

This landmark research was the product of an extensive international collaboration, drawing expertise from diverse fields including genetics, anthropology, archaeology, and bioinformatics. In addition to Elizabeth Nelson, Davide Bozzi, Anna-Sapfo Malaspinas, Miguel Delgado, and Lars Fehren-Schmitz, the research was co-led by Nasreen Broomandkhoshbacht, now at the University of Vermont. The broader team included Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a leading figure in paleopathology; Carlos Eduardo G. Amorim of California State University, Northridge; Melissa Estrada Pratt of the Instituto Colombiano de Antropología e Historia in Bogotá, Colombia, ensuring local archaeological expertise; Gilbert Greub of the University of Lausanne and Lausanne University Hospital in Switzerland, providing clinical and microbiological insights; Nicolas Rascovan of the Institut Pasteur in Paris, a specialist in ancient pathogen genomics; and David Šmajs of Masaryk University in the Czech Republic, a prominent researcher in Treponema genetics. This multidisciplinary and international effort underscores the complex nature of paleogenomic research and the necessity of bringing together varied perspectives to unravel the mysteries of our ancient past.