A lost disease emerges from 5,500-year-old human remains

The groundbreaking discovery pushes back the documented genetic history of Treponema pallidum by more than 3,000 years, offering compelling new evidence for the ancient presence and diversification of treponemal diseases in the Americas. The ancient DNA, extracted from a tibia found at a rock shelter near present-day Bogotá, represents a previously unknown lineage of the pathogen, suggesting a more complex and prolonged evolutionary journey for these diseases than previously understood. This revelation challenges long-held assumptions about the origins and global spread of conditions like syphilis, yaws, and bejel, particularly the hotly debated "Columbian Hypothesis."

Unearthing an Ancient Pathogen: A Serendipitous Discovery

The human remains, excavated from the renowned Tequendama 1 rock shelter, date back approximately 5,500 years, placing them firmly in the Late Archaic period of South American prehistory. This site, a crucial archaeological locality, has yielded extensive evidence of early human occupation and adaptation in the Andean highlands. Researchers, initially focused on studying ancient human population history, stumbled upon the bacterial genome during routine screening of deeply sequenced genetic data.

"The pathogen was not discovered intentionally at first," explained Davide Bozzi, a researcher at the University of Lausanne and SIB Swiss Institute of Bioinformatics, highlighting the serendipitous nature of the find. The team had generated an astonishing 1.5 billion fragments of genetic data from the individual, an unusually high yield that ultimately proved instrumental. During this extensive analysis, teams at the University of California, Santa Cruz, and the University of Lausanne independently detected traces of T. pallidum DNA, prompting a collaborative investigation into the unexpected presence of the ancient pathogen.

This unprecedented depth of sequencing allowed the scientists to reconstruct the complete bacterial genome without resorting to specialized enrichment techniques, which are often necessary to isolate pathogen DNA from the overwhelming amount of host genetic material. Furthermore, the recovery of the genome from a tibia—a shin bone—is notable. While T. pallidum infections can leave characteristic lesions on bones, the skeleton in question showed no visible evidence of disease. Most ancient T. pallidum genomes recovered to date have come from skeletal elements, such as teeth, that exhibited clear pathological markers. This success demonstrates that even bones without overt signs of infection can harbor invaluable genetic information about ancient diseases, opening new avenues for paleopathological research.

The Treponema pallidum Complex: A Family of Diverse Diseases

Treponema pallidum is a fascinating and medically significant spiral-shaped bacterium, known for its ability to cause a range of serious infectious diseases collectively referred to as treponematoses. Today, it exists in three closely related subspecies, each responsible for a distinct clinical manifestation:

• Treponema pallidum subspecies pallidum: Causes syphilis, a sexually transmitted infection that can progress through primary, secondary, latent, and tertiary stages, affecting multiple organ systems and potentially leading to severe neurological and cardiovascular complications.
• Treponema pallidum subspecies pertenue: Responsible for yaws, a chronic skin infection primarily affecting children in tropical and subtropical regions. It is typically transmitted through direct skin-to-skin contact.
• Treponema pallidum subspecies endemicum: The causative agent of bejel (also known as endemic syphilis), a non-venereal treponematosis found predominantly in arid regions of Africa and the Middle East, spreading through direct contact, often within families.

A fourth treponemal disease, pinta, is caused by Treponema carateum or Treponema pallidum subspecies carateum. Unlike its relatives, pinta is confined to the skin, causing discolored patches. A complete genome of the pathogen responsible for pinta has not yet been recovered, leaving gaps in our understanding of its evolutionary relationships and precise classification within the Treponema genus.

Despite their nearly identical genetic makeup—often sharing over 99.8% sequence identity—these subspecies exhibit remarkable differences in their modes of transmission, clinical symptoms, and geographical distribution. This genetic similarity juxtaposed with clinical diversity presents a formidable challenge for scientists attempting to unravel their evolutionary origins. While skeletal remains can sometimes offer clues to past infections, ancient DNA provides a far more precise and detailed narrative, filling crucial gaps between osteological evidence and the genetic reality of disease evolution.

Rewriting the Timeline: A Lost Lineage and Ancient Diversification

The most profound implication of the Colombian discovery lies in its radical re-calibration of the evolutionary timeline for treponemal pathogens. Researchers confirmed that the ancient DNA belonged to the species Treponema pallidum, but critically, it did not match any of the known modern disease-causing forms. This ancient genome represents a distinct "lost lineage" that split off very early in the bacterium’s evolutionary history, long before the divergence of the modern subspecies.

"In this study, researchers confirmed that the ancient DNA belonged to the species Treponema pallidum, but it did not match any of the known forms that cause disease today," said Anna-Sapfo Malaspinas, at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics. She added, "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. At this time, we cannot prove this is the case, but it is a lead worth investigating further."

Genetic analysis estimates that this ancient strain diverged from other T. pallidum lineages approximately 13,700 years ago. This astonishingly early date contrasts sharply with the estimated divergence of the three modern subspecies (syphilis, yaws, and bejel), which appear to have emerged much later, around 6,000 years ago. This timeline supports earlier research suggesting significant diversity among treponemal pathogens in the distant past and places the presence of these bacteria in the Americas firmly within the Late Pleistocene to early Holocene, a period corresponding to the major migrations of humans into the continent.

"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 Davide Bozzi. This extended timeline has significant implications for the long-standing debate surrounding the "Columbian Hypothesis," which posited that syphilis was introduced to Europe from the Americas by Columbus’s crew after 1492. While the ancient Colombian genome does not definitively resolve the origin of modern venereal syphilis, it provides strong evidence for a deep, pre-Columbian history of Treponema pallidum infections in the Americas, suggesting that treponemal diseases were not only present but diversifying long before European contact.

"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," stated Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU, underscoring the shift in perspective the new data offers.

The Paleogenomics Revolution: Insights into Human-Pathogen Co-evolution

The field of paleogenomics, the study of ancient DNA, has undergone a revolution in recent decades, transforming our understanding of evolutionary biology, human migration, and the co-evolution of humans and their pathogens. This study stands as a prime example of paleogenomics’ power. By retrieving and analyzing genetic material from long-deceased organisms, scientists can reconstruct evolutionary pathways, trace population movements, and gain unprecedented insights into the origins and spread of diseases.

"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," noted geneticist Lars Fehren-Schmitz at the University of California, Santa Cruz. This scientific discipline has moved beyond merely identifying ancient species to revealing intricate details of their genetic makeup, allowing for precise dating of evolutionary divergences and the identification of genetic adaptations in both hosts and pathogens.

The ability to recover pathogen genomes from skeletal remains, even those without visible lesions, expands the scope of paleogenomic investigations considerably. It suggests that many more ancient pathogen genomes may be preserved in archaeological collections than previously thought, waiting to be discovered through advanced sequencing techniques. This continuous refinement of ancient DNA extraction and sequencing methods promises an even richer understanding of the ancient microbial world and its interactions with human populations.

A Genetic Puzzle with Modern Implications

Tracing the origins and evolutionary paths of treponemal diseases remains an especially challenging "genetic puzzle." The bacteria’s extreme genetic similarity across subspecies, combined with their diverse transmission routes and vastly different clinical manifestations, makes their evolutionary history notoriously difficult to untangle. This complexity underscores the need for more ancient genomes to build a comprehensive picture.

The discovery at Tequendama 1 builds on extensive long-term archaeological and genetic work at the site. Earlier studies by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina and Fehren-Schmitz provided crucial background on the individual whose remains yielded the ancient T. pallidum genome. This collaborative, multidisciplinary approach, integrating archaeology, anthropology, and genetics, is fundamental to such complex investigations.

Understanding the deep history of infectious diseases is not merely an academic exercise; it has profound implications for modern public health. By learning how pathogens emerged, adapted, and spread in the past, scientists can better anticipate how they might evolve in the future. This knowledge is critical for developing more effective strategies for disease prevention, control, and treatment, helping societies prepare for potential future health threats, including the emergence of new strains or the re-emergence of old ones. The study of ancient pathogens provides a unique evolutionary laboratory, offering insights into long-term host-pathogen dynamics that are inaccessible through contemporary epidemiological studies alone.

Ethical Considerations and Community Engagement

The research team demonstrated a strong commitment to ethical practices and community engagement, an increasingly vital component of ancient DNA research, particularly when dealing with human remains from Indigenous territories. Before publishing their findings, the researchers proactively shared their results with communities in Colombia, recognizing the deep historical and cultural significance of the discovery.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," stated Miguel Delgado. The team consulted local scholars, students, and community members, engaging with stakeholders through presentations and interviews. All required permits for the export and study of the remains were meticulously obtained, ensuring adherence to national and international regulations.

"Engaging scholars, students, and Indigenous and non-Indigenous community members ensures the results are ethically communicated and interpreted in partnership with local communities," Delgado added. "This approach builds trust, supports responsible stewardship of sensitive discoveries, and reinforces local ownership of knowledge." This commitment to transparent and collaborative research is crucial for fostering respectful scientific inquiry and ensuring that the benefits of such discoveries are shared and understood by all stakeholders, especially the descendants of the populations being studied.

An International and Multidisciplinary Collaboration

The success of this complex research underscores the power of international and multidisciplinary collaboration. 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 research team brought together a diverse range of expertise, including Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a leading figure in bioarchaeology; 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; and David Šmajs of Masaryk University in the Czech Republic, a prominent expert in Treponema genomics. This formidable international consortium exemplifies the collaborative spirit required to tackle some of the most challenging questions in evolutionary medicine and human history.