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

The landmark discovery pushes back the confirmed 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. This ancient genome, recovered from human remains excavated from the Tequendama 1 rock shelter near present-day Bogotá, dates back approximately 5,500 years, placing it firmly in the Late Archaic period of the region. The implications of this finding are profound, offering new insights into the evolutionary timeline of human pathogens and challenging long-held assumptions about the origins and spread of diseases like syphilis.

"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 from the University of California, Santa Cruz, underscoring the interdisciplinary power of combining archaeology with cutting-edge genetic analysis.

Unraveling the Mystery of Treponemal Diseases

Treponema pallidum is a fascinating and elusive spiral-shaped bacterium, or spirochete, known for its ability to cause a range of debilitating diseases. Today, it exists in several closely related subspecies, each responsible for a distinct clinical syndrome. Treponema pallidum subspecies pallidum causes syphilis, a sexually transmitted infection with primary, secondary, latent, and tertiary stages that can affect virtually any organ system, leading to severe neurological, cardiovascular, and musculoskeletal complications if left untreated. Treponema pallidum subspecies pertenue causes yaws, a chronic skin and bone infection primarily affecting children in tropical and subtropical regions, transmitted through direct skin-to-skin contact. Treponema pallidum subspecies endemicum is responsible for bejel (also known as endemic syphilis), a non-venereal treponematosis found in arid regions, spread through non-sexual close contact, often sharing utensils. A fourth treponemal disease, pinta, is caused by Treponema carateum or Treponema pallidum subsp. carateum, characterized by skin lesions that change color over time. Crucially, no complete genome of the pathogen responsible for pinta has yet been recovered, leaving significant gaps in our understanding of its evolutionary relationships and classification within the treponemal family.

Despite their nearly identical genetic makeup, the diverse clinical presentations and transmission routes of these diseases have long puzzled scientists. The precise evolutionary mechanisms and timelines that led to the emergence of these different disease forms remain largely unknown. While skeletal remains can sometimes display tell-tale signs of chronic infection, such as periostitis or gummatous lesions, these markers are often non-specific and only appear in a fraction of infected individuals, leaving large gaps in the paleopathological record. This limitation highlights why ancient DNA (aDNA) analysis, or paleogenomics, is a critical tool for confirming the presence of pathogens and tracing their evolutionary trajectories.

A Lost Lineage and Ancient Divergence

The ancient DNA recovered in this study confirmed its classification as Treponema pallidum, yet it presented a unique genetic signature. Intriguingly, it did not precisely match any of the known modern forms that cause disease today. While closely related to contemporary strains, the ancient genome represents a distinct lineage that diverged very early in the bacterium’s evolutionary history. This discovery suggests a previously unknown diversity of treponemal pathogens in the ancient Americas.

Anna-Sapfo Malaspinas, from the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics, speculated on the potential identity of this ancient strain: "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." Pinta, known for its skin-localized symptoms and non-sexual transmission, aligns geographically with the discovery site, making it a plausible candidate for this ancestral lineage.

Genetic analysis allowed the researchers to estimate the divergence times of these treponemal lineages. This ancient strain is estimated to have separated from other T. pallidum lineages approximately 13,700 years ago, pushing the evolutionary timeline far into the Late Pleistocene. In stark contrast, the three modern subspecies (pallidum, pertenue, and endemicum) appear to have diverged much more recently, around 6,000 years ago. These timelines corroborate earlier research suggesting a deep and complex evolutionary history for treponemal pathogens and underscore the significant genetic diversification that occurred long before the advent of modern humans’ major migratory movements.

"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 nuanced perspective is crucial, as the presence of an ancient Treponema pallidum strain does not automatically confirm the presence of syphilis as we know it today, but rather its bacterial ancestor or a related treponemal infection.

Rewriting the "Columbian Exchange" Narrative

The origins of treponemal diseases, particularly syphilis, have been a subject of intense historical and scientific debate for centuries. The "Columbian Exchange" hypothesis posits that syphilis was brought to Europe from the Americas by Christopher Columbus’s returning crew in the late 15th century, leading to a widespread epidemic in the Old World. Conversely, the "pre-Columbian" hypothesis suggests that treponemal diseases, including syphilis, were present in Europe prior to Columbus’s voyages, or that a milder form of treponematosis evolved into the more virulent syphilis strain in the Old World.

Tracing these origins is exceptionally challenging due to the bacteria’s extreme genetic similarity across subspecies, coupled with their vastly different transmission modes and clinical manifestations. The current discovery from Colombia provides robust paleogenomic evidence that a diverse Treponema pallidum lineage was well-established in the Americas thousands of years before any European contact. This finding significantly strengthens the argument for an ancient, pre-Columbian presence of treponemal infections in the New World, adding substantial weight to the "Columbian Exchange" theory regarding the origin of the bacterial family, even if it doesn’t definitively pinpoint the exact emergence of syphilis pallidum itself.

"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 researcher Davide Bozzi from the University of Lausanne and SIB Swiss Institute of Bioinformatics. This extended timeline implies a deep co-evolutionary history between T. pallidum and human populations in the Americas, challenging any notion of a recent introduction of the entire bacterial family to the continent.

Paleogenomics: Unlocking Ancient Secrets from a Tibia

The discovery builds upon extensive long-term archaeological and genetic work at the Tequendama 1 site, a crucial location for understanding early human occupation in the Andean region. Previous studies by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina and Fehren-Schmitz provided detailed background on the human remains themselves, setting the stage for this groundbreaking genetic investigation.

Remarkably, the pathogen was not discovered intentionally at first. Researchers initially sequenced the individual’s DNA with the primary goal of studying ancient human population history in the region. This ambitious undertaking generated an extraordinary volume of genetic data—approximately 1.5 billion fragments—far exceeding the typical yield for ancient DNA studies. During routine screening of this massive dataset, teams at the University of California, Santa Cruz, and the University of Lausanne independently detected minute traces of T. pallidum DNA. Recognizing the immense significance of this unexpected find, the two teams decided to collaborate and investigate further.

The technical achievement of reconstructing a pathogen’s genome from such a small fraction of the total genetic material is noteworthy. While bacterial DNA made up only a tiny portion of the 1.5 billion fragments, the sheer depth of sequencing allowed the team to assemble the pathogen’s genome without the need for specialized enrichment techniques—a common and often necessary step in ancient pathogen detection. This demonstrates the power of high-throughput sequencing and advanced bioinformatics in uncovering hidden biological narratives.

Traditionally, the diseases caused by T. pallidum (bejel, yaws, and syphilis) are known to leave characteristic marks on bones, but only under certain conditions and not in all infected individuals. Most ancient genomes of this bacterium recovered to date have come from teeth or bones that clearly showed visible signs of disease. However, in this groundbreaking case, the skeleton from Tequendama 1 showed no visible evidence of infection. Researchers sampled a tibia, or shin bone, which is not commonly used for ancient DNA studies, particularly for pathogen detection. The success of this unconventional approach suggests that even bones without obvious pathological markers can preserve invaluable genetic information, opening new avenues for future paleogenomic research and disease detection.

The Tequendama 1 Site: A Window into Prehistoric Colombia

The Tequendama 1 rock shelter, located in the Sabana de Bogotá region, is a significant archaeological site that has yielded critical insights into the early human inhabitants of the Colombian Andes. Situated at an altitude of approximately 2,570 meters (8,430 feet) above sea level, the site provides evidence of human occupation dating back over 10,000 years, making it one of the oldest archaeological sites in Colombia. The remains from which the T. pallidum genome was reconstructed belong to an individual from a period characterized by hunter-gatherer societies adapting to the highland environment.

The meticulous archaeological work at Tequendama 1, spanning decades, has provided a rich context for understanding the lifeways, diet, and health of these ancient populations. The discovery of the Treponema pallidum genome within these remains adds a crucial layer to this understanding, painting a more complete picture of the challenges and diseases faced by these early inhabitants. It underscores that infectious diseases were an integral part of human experience long before the advent of agriculture or dense urban centers.

Why Ancient Disease History Matters Today

Understanding how infectious diseases emerged and evolved in the past holds profound implications for modern public health. By tracing the evolutionary pathways of pathogens like Treponema pallidum, scientists can gain a deeper appreciation for the adaptive strategies of bacteria, the dynamics of host-pathogen interactions, and the environmental factors that influence disease emergence and spread. This knowledge is not merely academic; it can help anticipate how pathogens might evolve in the future, how they might respond to treatments, and how new diseases could emerge. Such insights are invaluable for developing more effective prevention strategies, diagnostic tools, and therapeutic interventions for current and future health threats.

The ongoing challenges posed by emerging infectious diseases, antibiotic resistance, and re-emerging pathogens make paleogenomics an increasingly vital field. By providing a deep-time perspective on pathogen evolution, it equips modern societies with historical context to better prepare for potential health crises.

Ethical Research and Community Engagement

A critical aspect of this research, emphasized by the team, was the ethical framework employed. Before publishing their findings, the research team made a concerted effort to share their discoveries with communities in Colombia. This engagement recognized the deep connection of the findings to the country’s medical and cultural history. They consulted with local scholars, students, and community members, including Indigenous and non-Indigenous groups, through presentations and interviews. All required permits for the export and study of the human remains were meticulously obtained, adhering to international and national regulations.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," highlighted Miguel Delgado. "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 and responsible stewardship serves as a model for future paleogenomic and archaeological research involving human remains, particularly in regions with rich cultural heritage.

An International Collaborative Endeavor

The success of this complex research project is a testament to international collaboration and interdisciplinary expertise. In addition to Nelson, Bozzi, Malaspinas, Delgado, and 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; Carlos Eduardo G. Amorim of California State University, Northridge; Melissa Estrada Pratt of the Instituto Colombiano de Antropología e Historia in Bogotá, Colombia; Gilbert Greub of the University of Lausanne and Lausanne University Hospital in Switzerland; Nicolas Rascovan of the Institut Pasteur in Paris; and David Šmajs of Masaryk University in the Czech Republic. This extensive list of contributors from diverse institutions across multiple continents underscores the global nature of scientific inquiry and the collaborative spirit required to unlock such profound secrets from humanity’s ancient past. The findings represent a significant step forward in our understanding of human disease history and the power of ancient DNA to illuminate the hidden evolutionary stories of our pathogens.