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

This bacterium is responsible for several serious infectious diseases today, including syphilis. The findings, published in the prestigious journal Science, significantly expand what researchers know about how long these infections have affected human populations, pushing back the known genetic history of Treponema pallidum by more than 3,000 years and challenging long-held assumptions about the origins and spread of treponemal diseases in the Americas.

A Groundbreaking Discovery at Tequendama 1

The ancient human remains, from which the pathogen’s genetic material was extracted, were meticulously excavated from the Tequendama 1 rock shelter, a significant archaeological site located near present-day Bogotá. This site has long been a focal point for understanding early human occupation in the Andean region of Colombia, providing invaluable insights into prehistoric life, diets, and cultural practices. The specific individual from whom the Treponema pallidum genome was recovered dates back roughly 5,500 years Before Present (BP), placing them firmly in the Late Archaic period of South American prehistory.

The identification of this ancient genome represents a monumental leap in paleogenomics, extending the known genetic history of Treponema pallidum from a previous benchmark of around 2,000-3,000 years to an astonishing 5,500 years. This substantial temporal extension adds considerable weight to the growing body of evidence suggesting that treponemal diseases were circulating and diversifying in the Americas far earlier than previously documented, significantly predating European contact.

Lars Fehren-Schmitz, a geneticist at the University of California, Santa Cruz, and a co-lead author of the study, emphasized the broader implications of the research. "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," Fehren-Schmitz stated, highlighting the power of ancient DNA to unravel complex evolutionary narratives.

Understanding Treponemal Diseases: A Diverse and Ancient Family

Treponema pallidum is a fascinating and medically significant spiral-shaped bacterium, or spirochete, that manifests today in several closely related subspecies, each responsible for distinct diseases. The most widely known is Treponema pallidum subspecies pallidum, the causative agent of syphilis, a sexually transmitted infection with widespread systemic effects if left untreated. Another subspecies, Treponema pallidum subspecies pertenue, causes yaws, a chronic, disfiguring skin disease primarily affecting children in tropical and subtropical regions, spread through non-sexual skin-to-skin contact. The third major subspecies, Treponema pallidum subspecies endemicum, is responsible for bejel (also known as endemic syphilis), an infection transmitted non-sexually through direct contact, often oral, and prevalent in arid regions.

A fourth treponemal disease, pinta, is caused by Treponema carateum, sometimes classified as Treponema pallidum subspecies carateum. Pinta is characterized by skin lesions and disfiguring changes, typically found in Central and South America. Historically, it has been less studied at the genetic level; no complete genome of the pathogen responsible for pinta has yet been recovered, leaving significant gaps in our understanding of its evolutionary relationships and precise taxonomic classification. This lack of a complete genetic blueprint makes the discovery of an ancient, distinct lineage particularly intriguing for pinta research.

Despite their remarkably similar genetic makeup – often sharing over 99% sequence identity – scientists still grapple with understanding the precise timelines and mechanisms through which these different disease forms emerged and diverged. While skeletal remains can sometimes provide clues, showing signs of infection like periostitis or gummatous lesions, such evidence is often non-specific and inconsistent. Genetics, specifically the analysis of ancient DNA (aDNA), offers a far more precise and complex story, bridging the large gaps between what bones can reveal and what ancient genetic material can definitively confirm about pathogen evolution.

A Lost Lineage of a Familiar Pathogen: Deeper Evolutionary Roots

The study’s most compelling revelation is that the ancient DNA recovered from the Colombian remains belonged to the species Treponema pallidum, yet it did not precisely match any of the known modern forms that cause disease today. This ancient genome, while closely related to contemporary strains, appears to represent a distinct lineage that split off very early in the bacterium’s evolutionary history.

"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," commented Anna-Sapfo Malaspinas at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics. She added a note of scientific caution, "At this time, we cannot prove this is the case, but it is a lead worth investigating further." This hypothesis opens new avenues for understanding pinta’s origins and its place within the broader Treponema pallidum family tree.

Based on detailed genetic analysis and phylogenetic reconstruction, scientists estimate that this ancient strain diverged from other T. pallidum lineages approximately 13,700 years ago. This timeline is starkly contrasted with the divergence of the three modern subspecies (syphilis, yaws, and bejel), which appear to have separated much more recently, around 6,000 years ago. These chronological markers provide strong support for earlier research suggesting significant diversity among treponemal pathogens in the distant past, long before the historical period.

Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU and a co-author on the study, contextualized these findings within the ongoing scientific discourse. "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," Nelson explained. This nuance is critical; while the specific origin of each disease syndrome (e.g., syphilis) remains debated, the presence and diversification of the Treponema pallidum species in the Americas well before the Columbian Exchange is now firmly established genetically.

A Genetic Puzzle with Modern Implications: Re-evaluating Disease History

Tracing the origins and evolutionary paths of treponemal diseases has always been an immense challenge. The bacteria are remarkably similar at the genetic level, making fine-grained distinctions difficult. Yet, they spread through different modes of transmission (sexual, skin-to-skin, oral) and can cause profoundly different clinical symptoms, further complicating efforts to untangle their evolutionary trajectories.

"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," stated Davide Bozzi, a researcher at the University of Lausanne and SIB Swiss Institute of Bioinformatics. This timeframe places the co-existence of T. pallidum with humans potentially during or shortly after the initial peopling of the Americas, suggesting a deep and intricate co-evolutionary history on the continent. Such early divergence implies that Treponema pallidum may have journeyed with some of the earliest human migrants into the Americas, adapting and diversifying alongside human populations over millennia.

The discovery builds significantly on extensive long-term archaeological and genetic work conducted at the Tequendama 1 site. Earlier studies, led by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina and geneticist Lars Fehren-Schmitz, had already provided detailed background and anthropological context for the skeleton itself, laying the groundwork for this remarkable paleogenomic investigation.

An Unexpected Find in Massive DNA Data: The Power of Serendipity and Scale

Remarkably, the ancient Treponema pallidum pathogen was not the initial target of the DNA sequencing efforts. Researchers were primarily focused on sequencing the individual’s DNA to investigate ancient human population history in the region, aiming to understand migration patterns and genetic diversity. This ambitious project generated an enormous dataset: approximately 1.5 billion fragments of genetic data, a volume far exceeding what is typically obtained in ancient DNA studies.

During routine screening and bioinformatics analysis, teams at the University of California, Santa Cruz, and the University of Lausanne independently detected minute but undeniable traces of Treponema pallidum DNA. Recognizing the profound potential of this unexpected finding, the two research groups decided to pool their expertise and collaborate on a joint investigation to reconstruct the pathogen’s genome.

Despite the fact that bacterial DNA constituted only a tiny fraction of the total genetic material – a common challenge in ancient pathogen studies where host DNA overwhelmingly dominates – the sheer depth and quality of the sequencing data proved sufficient. This allowed the team to reconstruct a nearly complete Treponema pallidum genome without the need for specialized enrichment techniques, which are often employed to increase the proportion of pathogen DNA in a sample. This highlights the growing sophistication of paleogenomic methods and the capacity to extract meaningful information from even very low-abundance ancient pathogens.

A crucial aspect of this discovery relates to paleopathology. The diseases caused by T. pallidum (bejel, yaws, and syphilis) can leave characteristic marks on bones, but only under specific conditions and not in all infected individuals. Historically, most ancient genomes of this bacterium have been recovered from skeletal elements like teeth or bones that clearly exhibited macroscopic signs of disease. In stark contrast, the Tequendama 1 skeleton showed no visible evidence of treponemal infection. Furthermore, researchers sampled a tibia, or shin bone, which is not as commonly used for ancient DNA studies as teeth or petrous bones due to lower DNA preservation rates. The success of this innovative approach suggests that even bones without obvious disease markers can preserve invaluable genetic information, opening up new avenues for screening ancient human remains for hidden pathogens.

Why Ancient Disease History Matters Today: Preparing for Future Threats

The study of ancient infectious diseases, or paleomicrobiology, is far more than a historical exercise. By meticulously learning how infectious diseases emerged, evolved, and changed in the distant past, scientists gain critical insights into the fundamental evolutionary mechanisms of pathogens. This knowledge is directly applicable to understanding how modern pathogens might adapt, develop drug resistance, or give rise to new variants in the future. Such foresight could prove invaluable in helping modern societies prepare for and mitigate potential future health threats, from emerging infectious diseases to antibiotic-resistant strains.

Beyond its immediate scientific impact, the research team demonstrated a deep commitment to ethical scientific practice and community engagement. Before publishing their groundbreaking results, the research team proactively shared their findings with communities in Colombia. This included consulting local scholars, students, and community members, as well as engaging with stakeholders through presentations and interviews. All required permits for the export and study of the ancient human remains were meticulously obtained, adhering to national and international legal and ethical guidelines.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," explained Miguel Delgado, the archaeologist who led the original excavations. "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 collaborative and culturally sensitive research sets a high standard for paleogenomic studies involving human remains.

An International Collaboration Driving Scientific Advancement

The monumental achievement of reconstructing this ancient Treponema pallidum genome was the result of a truly international and interdisciplinary 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 scientific team comprised a diverse group of experts from various institutions and countries. This included Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a pioneer 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 expertise; Gilbert Greub of the University of Lausanne and Lausanne University Hospital in Switzerland; Nicolas Rascovan of the Institut Pasteur in Paris, a leading center for infectious disease research; and David Šmajs of Masaryk University in the Czech Republic, a specialist in Treponema genetics. This extensive network of collaborators underscores the complex, multi-faceted nature of paleogenomic research and the global scientific effort required to unlock such profound insights into human and pathogen history.

This discovery not only rewrites a significant chapter in the history of infectious diseases but also exemplifies the transformative power of paleogenomics. By meticulously piecing together the genetic fragments of ancient pathogens, scientists are gaining unprecedented clarity into the deep past, offering invaluable perspectives that resonate with the health challenges and scientific inquiries of the present day. The ancient Treponema pallidum from the Sabana de Bogotá stands as a testament to humanity’s long and complex relationship with disease, a relationship that continues to shape our understanding of life itself.