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

The ancient human remains were meticulously excavated from a rock shelter near present-day Bogotá, a site known as Tequendama 1, which holds significant archaeological importance for understanding early human occupation in the high-altitude plateaus of the northern Andes. Dating back approximately 5,500 years, this individual’s bones harbored a silent genetic secret that has now profoundly altered the timeline of human disease. By identifying and reconstructing this ancient bacterial genome, researchers have not only extended the known genetic lineage of Treponema pallidum but have also unveiled a previously unknown branch of its evolutionary tree, offering a unique window into the pathogen’s diversification long before the advent of recorded history.

"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," affirmed geneticist Lars Fehren-Schmitz at the University of California, Santa Cruz, a co-leader of the study. This statement underscores the transformative power of ancient DNA analysis, not merely as an academic exercise but as a crucial tool for public health and evolutionary biology, enabling scientists to trace the origins and spread of diseases that continue to impact millions globally.

Unveiling the Treponemal Family: A Global Health Challenge

Treponema pallidum is a fascinating and formidable spiral-shaped bacterium, known for its ability to cause a spectrum of treponemal diseases. Today, it exists primarily in three closely related subspecies, each responsible for a distinct clinical manifestation: Treponema pallidum subspecies pallidum causes syphilis, a sexually transmitted infection with widespread systemic effects; Treponema pallidum subspecies pertenue is the causative agent of yaws, a chronic skin, bone, and cartilage disease primarily affecting children in tropical and subtropical regions; and Treponema pallidum subspecies endemicum leads to bejel (or endemic syphilis), a non-venereal disease characterized by skin and oral lesions, prevalent in arid areas. A fourth treponemal disease, pinta, caused by Treponema carateum (sometimes classified as Treponema pallidum subspecies carateum), primarily affects the skin with disfiguring lesions, particularly in Central and South America. Historically, these diseases have posed immense public health challenges, and despite significant medical advancements, they continue to be a concern, especially in vulnerable populations.

Despite their remarkably similar genetic makeup, the precise timing and mechanisms by which these different disease forms emerged remain largely unknown, representing a significant puzzle in medical history. While skeletal remains can sometimes display tell-tale signs of long-term infection, such as characteristic bone lesions, genetic evidence often reveals a more intricate and ancient narrative. Large gaps have historically existed between what osteoarchaeological evidence can suggest and what ancient DNA analysis can definitively confirm about the deep evolutionary history of pathogens. The current study bridges a substantial portion of this gap, providing concrete genetic proof of an ancient treponemal infection in the Americas.

A Lost Lineage: The Colombian Discovery

A key revelation of this study is that the ancient DNA recovered from the Colombian remains, while undeniably belonging to the species Treponema pallidum, did not precisely match any of the known modern forms that cause disease today. This ancient genome represents a distinct lineage that diverged early in the bacterium’s evolutionary history, indicating a previously uncharacterized branch of the treponemal family tree. Although closely related to contemporary strains, its unique genetic signature suggests it represents an evolutionary "ghost lineage" – a form that existed in the distant past but may no longer be circulating or has evolved significantly into other forms.

"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," speculated Anna-Sapfo Malaspinas at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics. She emphasized, "At this time, we cannot prove this is the case, but it is a lead worth investigating further." This hypothesis opens exciting avenues for future research, particularly concerning the evolutionary relationship between the distinct treponemal diseases and their geographical distribution.

Based on comprehensive genetic analysis and molecular clock dating, scientists estimate that this ancient strain separated from other T. pallidum lineages approximately 13,700 years ago, placing its divergence firmly in the Late Pleistocene epoch. In stark contrast, the three modern subspecies responsible for syphilis, yaws, and bejel appear to have diverged much more recently, around 6,000 years ago. These divergent timelines are crucial; they not only support earlier research suggesting the deep antiquity of treponemal pathogens but also highlight the considerable genetic diversity that existed within the Treponema pallidum species in the distant past, long before the major demographic shifts associated with agricultural revolutions and global expansions.

"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, succinctly capturing the essence of the finding’s impact on a persistent scientific debate.

The "Columbian Hypothesis" Reimagined: Tracing Origins

The origin of syphilis, in particular, has been a subject of fervent debate among historians and scientists for centuries. The "Columbian Hypothesis" posits that syphilis was brought to Europe from the New World by Christopher Columbus’s returning crew in the late 15th century, leading to a devastating epidemic. Conversely, the "Pre-Columbian Hypothesis" argues that treponemal diseases, or at least forms closely related to syphilis, already existed in the Old World before Columbus’s voyages, or that the New World simply hosted its own diverse array of treponemal pathogens. The discovery of a 5,500-year-old Treponema pallidum genome in the Americas provides compelling genetic evidence for the ancient presence of treponemal diseases in the continent, significantly strengthening the argument for a deep, pre-Columbian history of these pathogens in the New World. While it doesn’t definitively prove whether syphilis as we know it today originated there, it irrevocably demonstrates that the evolutionary roots of the Treponema pallidum family run far deeper in the Americas than previously established, complicating simplistic narratives of disease transmission tied solely to post-Columbian contact.

A Genetic Puzzle with Modern Implications

Tracing the evolutionary origins of treponemal diseases presents a formidable challenge because the bacteria are remarkably similar at the genetic level, even while they manifest in distinct ways, spread through different routes (sexual, skin-to-skin, oral), and cause vastly different symptoms. This phenotypic plasticity despite genetic homogeneity makes their evolutionary paths particularly difficult to untangle, highlighting the need for ancient DNA studies to resolve these complex relationships.

"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 extension into the Late Pleistocene suggests that Treponema pallidum may have co-evolved with human populations for a period far longer than previously appreciated, potentially dating back to early migrations into the Americas.

This monumental discovery is the culmination of extensive, long-term archaeological and genetic work at the Tequendama 1 site. Earlier studies conducted by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina, in collaboration with Fehren-Schmitz, had already provided detailed background and context for the human skeleton from which the ancient DNA was extracted, laying the groundwork for this pivotal paleogenomic investigation.

An Unexpected Find in Massive DNA Data: The Power of Paleogenomics

Remarkably, the ancient pathogen was not initially discovered through targeted searching. Researchers had originally sequenced the individual’s DNA with the primary goal of studying ancient human population history and migration patterns in the Americas. This ambitious undertaking generated an extraordinary volume of genetic data – approximately 1.5 billion fragments of DNA – far more extensive than typically obtained in such studies. During routine screening and analysis of this massive dataset, research teams at the University of California, Santa Cruz, and the University of Lausanne independently detected minute but unmistakable traces of Treponema pallidum. Recognizing the immense significance of this unexpected finding, the two teams promptly decided to collaborate and investigate further.

Despite bacterial DNA constituting only a tiny fraction of the total genetic material recovered from the human remains, the sheer depth of sequencing achieved enabled the team to reconstruct the pathogen’s complete genome without resorting to specialized enrichment techniques, which are often necessary to isolate and amplify microbial DNA from ancient samples. This methodological success highlights the growing power of high-throughput sequencing technologies and sophisticated bioinformatics tools in paleogenomics, demonstrating that even subtle genetic signatures can yield revolutionary insights when data acquisition is sufficiently robust.

Furthermore, another significant aspect of this discovery is that the human skeleton showed no visible evidence of treponemal infection. Diseases caused by T. pallidum (bejel, yaws, and syphilis) can leave characteristic marks on bones, but these lesions only develop under specific conditions and are not universally present in all infected individuals. Most ancient genomes of this bacterium recovered to date have come from skeletal elements, such as teeth or bones, that clearly displayed macroscopic signs of disease. In this instance, researchers sampled a tibia, or shin bone – a bone not traditionally favored for ancient DNA studies, particularly when no visible pathology is present. The successful recovery of a complete pathogen genome from a non-diseased tibia suggests that even human remains without overt signs of infection can preserve invaluable genetic information about past disease landscapes, opening new avenues for paleopathological research and expanding the potential scope of ancient DNA investigations.

Why Ancient Disease History Matters Today: Implications for Future Health

Understanding how infectious diseases emerged, diversified, and adapted in the past is not merely an academic pursuit; it holds profound implications for contemporary public health. By unraveling the evolutionary trajectories of pathogens like Treponema pallidum, scientists can gain critical insights into the fundamental mechanisms of host-pathogen co-evolution, genetic resilience, and adaptation. This knowledge can, in turn, help to better anticipate how current and future infectious diseases might evolve, spread, and potentially pose new threats to human populations. Such historical perspective is invaluable for developing more effective strategies for disease surveillance, prevention, and treatment, thereby bolstering modern societies’ preparedness for potential health crises.

Beyond the scientific revelations, the research team demonstrated a deep commitment to ethical research practices and community engagement. Before publishing their findings, the researchers proactively shared their results with communities in Colombia, acknowledging the profound importance of this discovery to the country’s medical, cultural, and historical heritage. This engagement involved extensive consultations with local scholars, students, and both Indigenous and non-Indigenous community members, fostering dialogue through presentations and interviews with various stakeholders. All necessary permits for the excavation, export, and study of the human remains were meticulously obtained, ensuring strict adherence to international ethical guidelines and national regulations.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," explained Miguel Delgado, emphasizing the critical role of local collaboration. "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 collaborative and ethically grounded approach sets a benchmark for future paleogenomic studies, particularly those involving human remains and culturally significant discoveries.

An International Collaborative Endeavor

The success of this ambitious project underscores the inherently collaborative nature of modern scientific research, drawing together expertise from diverse disciplines and institutions across the globe. In addition to the lead researchers previously mentioned – Elizabeth Nelson, Davide Bozzi, Anna-Sapfo Malaspinas, Miguel Delgado, and Lars Fehren-Schmitz – the research was also co-led by Nasreen Broomandkhoshbacht, now at the University of Vermont.

The broader international team comprised a distinguished group of scientists, including Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a world-renowned bioarchaeologist; 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, contributing microbiology 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 leading expert on Treponema pallidum genetics. This multidisciplinary and international collaboration was instrumental in achieving such a groundbreaking reconstruction, pushing the boundaries of what is known about human disease history and setting new standards for ethical engagement in paleogenomic research.