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

The landmark discovery, detailed in a recent issue of the prestigious journal Science, pushes back the known genetic history of Treponema pallidum by more than 3,000 years. This ancient genome, recovered from human remains excavated from a rock shelter near present-day Bogotá, provides compelling evidence that treponemal diseases have circulated in the Americas far earlier than previously documented, challenging long-held assumptions about their origins and global spread. The meticulous paleogenomic analysis reveals a previously unknown lineage of this pervasive pathogen, offering unprecedented insights into its evolutionary journey and its deep association with human populations in the Late Pleistocene and early Holocene epochs.

A Glimpse into Ancient Pathogens: Treponema pallidum and Its Kin

Treponema pallidum is a spiral-shaped bacterium, infamous for causing a range of debilitating diseases. Today, it is primarily recognized through three closely related subspecies, each responsible for a distinct illness: Treponema pallidum subspecies pallidum causes syphilis, a sexually transmitted infection with devastating systemic effects; Treponema pallidum subspecies pertenue is the agent of yaws, a chronic skin, bone, and joint infection prevalent in tropical and subtropical regions; and Treponema pallidum subspecies endemicum leads to bejel (or endemic syphilis), a non-venereal disease primarily affecting skin, mucous membranes, and bones in arid regions. A fourth treponemal disease, pinta, caused by Treponema carateum or Treponema pallidum subspecies carateum, primarily affects the skin with disfiguring lesions. Notably, a complete genome of the pathogen responsible for pinta has yet to be recovered, leaving significant gaps in our understanding of its evolutionary relationships and precise classification.

Despite their nearly identical genetic makeup, the precise timelines and mechanisms by which these different disease forms emerged remain a subject of intense scientific debate. While skeletal remains can sometimes bear tell-tale signs of infection, such as periosteal reactions or gummatous lesions, ancient DNA often reveals a far more complex and nuanced story. Large gaps have historically existed between the osteological evidence gleaned from bones and the definitive genetic confirmation required to trace disease evolution accurately. This latest research bridges some of these gaps, providing a critical genetic anchor point in the deep past.

The Colombian Connection: Unearthing a Lost Lineage

The human remains from which the ancient Treponema pallidum genome was reconstructed were unearthed from the Tequendama 1 site, a significant rock shelter located in the Sabana de Bogotá. This archaeological site has been a focal point for understanding ancient human occupation and environmental changes in the region for decades. The individual, an adult male, dates back approximately 5,500 years, placing him squarely in the mid-Holocene period, long before established historical records.

"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," remarked geneticist Lars Fehren-Schmitz at the University of California, Santa Cruz, one of the study’s lead authors. His statement underscores the transformative power of ancient DNA research in reshaping our comprehension of disease history.

The ancient DNA recovered from the Colombian individual unequivocally belonged to the species Treponema pallidum. However, to the surprise of researchers, this ancient genome did not precisely match any of the known modern forms that cause disease today. Instead, while closely related to contemporary 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 genetic diversity among ancient treponemal pathogens than previously understood.

Anna-Sapfo Malaspinas, at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics, offered a compelling hypothesis: "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." She added, "At this time, we cannot prove this is the case, but it is a lead worth investigating further." This speculation opens new avenues for research into the less-understood treponematoses and their deep evolutionary roots in the Americas.

Rewriting the Evolutionary Timeline

Based on sophisticated genetic analysis, scientists estimate that this ancient Colombian strain separated from other T. pallidum lineages approximately 13,700 years ago. This dating places its divergence squarely in the Late Pleistocene epoch, a period coinciding with significant human migrations across the Bering Strait into the Americas. In stark contrast, the three modern subspecies (syphilis, yaws, and bejel) appear to have diverged much later, around 6,000 years ago. These timelines provide crucial support for earlier research suggesting a deep and diverse history of treponemal pathogens in the Americas, pushing their association with humans potentially beyond 10,000 years ago.

"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. Her comments highlight the critical distinction between the evolutionary history of the pathogen and the emergence of specific disease syndromes, emphasizing the complexity of untangling these threads.

The implications for the "Columbian Exchange" debate, which posits whether syphilis originated in the Americas and was brought to Europe by Columbus’s crew or vice versa, are profound. While this specific ancient strain is not directly ancestral to modern venereal syphilis, its presence in the Americas at such an ancient date strongly supports the notion of a long-standing and diverse pool of treponemal pathogens in the New World. This evidence significantly strengthens the argument for an American origin for at least some forms of treponemal disease, predating European contact by millennia.

An Unexpected Find in Massive DNA Data

The discovery of the ancient Treponema pallidum genome was, in many ways, serendipitous. Researchers were not initially searching for ancient pathogens. Instead, they were sequencing the individual’s DNA to study ancient human population history, generating an astonishing 1.5 billion fragments of genetic data – a volume far exceeding typical ancient DNA sequencing projects. It was during routine screening of this massive dataset that teams at the University of California, Santa Cruz, and the University of Lausanne independently detected faint but unmistakable traces of T. pallidum. Recognizing the immense potential of this unexpected finding, the two teams decided to collaborate and investigate further.

Crucially, despite the bacterial DNA making up only a tiny fraction of the total genetic material, the sheer depth of sequencing allowed the team to reconstruct a near-complete pathogen genome without the need for specialized enrichment techniques typically employed to boost target DNA concentrations. This methodological success underscores the power of high-throughput sequencing and advanced bioinformatics in paleogenomics.

Furthermore, the researchers sampled a tibia, or shin bone, for their analysis – a bone not commonly favored for ancient DNA studies due to its lower preservation potential compared to petrous bone (inner ear) or teeth. What makes this even more remarkable is that the skeleton showed no visible osteological evidence of infection. Traditionally, most ancient pathogen genomes of T. pallidum have been recovered from teeth or bones that clearly exhibited signs of disease. The success of this approach suggests that even skeletal elements without obvious disease markers can preserve invaluable genetic information, opening new avenues for future paleopathological investigations and expanding the scope of recoverable ancient pathogen DNA.

A Genetic Puzzle with Modern Implications

Tracing the origins and evolutionary paths of treponemal diseases presents a unique challenge to scientists. The bacteria are remarkably similar at the genetic level, making it difficult to differentiate subspecies and trace their evolutionary divergences. At the same time, they spread through diverse mechanisms – sexual contact, skin-to-skin contact, or congenital transmission – and can cause a wide spectrum of symptoms, from debilitating systemic illness to localized skin lesions. This intricate interplay of genetic similarity, varied transmission routes, and diverse clinical presentations makes their evolutionary histories particularly difficult to untangle.

The groundbreaking work at Tequendama 1 builds on a long history of archaeological and genetic research. Earlier studies by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina and Fehren-Schmitz provided crucial background on the individual skeleton, setting the stage for this genetic breakthrough. Their foundational work ensured that the context of the discovery was meticulously understood, enhancing the scientific rigor of the paleogenomic analysis.

Why Ancient Disease History Matters Today

The study of ancient diseases, known as paleopathology and paleogenomics, is not merely an academic exercise. By learning how infectious diseases emerged, adapted, and changed in the distant past, scientists gain critical insights into the fundamental principles of pathogen evolution. This knowledge is invaluable for better anticipating how modern pathogens might evolve in the future, how they might jump between hosts, or how they could develop resistance to existing treatments. This deep historical perspective can significantly inform contemporary public health strategies, helping societies prepare for and mitigate potential future health threats, including emerging infectious diseases or re-emerging historical scourges. Understanding the long co-evolutionary history of humans and their pathogens is a cornerstone of global health security.

Ethical Stewardship and Community Engagement

Before publishing their results, the research team demonstrated exemplary ethical conduct by sharing their findings with communities in Colombia. Recognizing the profound historical, medical, and cultural significance of the discovery to the country, they engaged in extensive consultations with local scholars, students, and community members. This engagement included presentations and interviews with various stakeholders, ensuring that the research was not only scientifically sound but also socially responsible. All required permits for the export and study of the ancient human remains were meticulously obtained, adhering to international and national ethical guidelines.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," stated Miguel Delgado. He further elaborated, "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 high standard for future paleogenomic research, emphasizing the importance of collaborative and respectful partnerships when dealing with human remains and cultural heritage.

An International Collaborative Effort

The success of this complex paleogenomic endeavor is a testament to international scientific 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, multidisciplinary 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 diverse group of geneticists, anthropologists, paleopathologists, and bioinformaticians from multiple institutions across several continents underscores the collaborative spirit required to unlock the secrets of our ancient past and shed new light on the enduring mysteries of human disease.