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

This landmark paleogenomic discovery pushes back the known genetic history of Treponema pallidum by more than 3,000 years, offering unprecedented insights into the deep evolutionary past of treponemal diseases in the Americas. The ancient genome, extracted from an individual buried in a rock shelter near present-day Bogotá, provides compelling evidence that a diverse array of treponemal pathogens circulated on the continent far earlier than previously documented, challenging long-held assumptions about their origins and spread.

The Tequendama 1 Site: A Window into Ancient Americas

The human remains at the heart of this study were excavated from the renowned Tequendama 1 rock shelter, an archaeological site of immense significance located approximately 30 kilometers southwest of Bogotá, Colombia. For decades, Tequendama 1 has served as a crucial locale for understanding the peopling of the Americas and the lifeways of early hunter-gatherer communities in the Andean highlands. Archaeological investigations, particularly those led by scholars like Miguel Delgado of the Universidad Nacional de La Plata in Argentina, have unearthed a rich trove of human remains, tools, and faunal evidence dating back over 10,000 years. These findings paint a picture of early inhabitants adapting to diverse environments, utilizing varied subsistence strategies, and developing complex cultural practices.

The specific individual from whom the Treponema pallidum genome was recovered dates back roughly 5,500 years, placing them firmly within the Late Archaic period of South American prehistory. This era was characterized by increasing population densities, regional adaptations, and the beginnings of more settled lifestyles, albeit still predominantly foraging-based. The meticulous archaeological work at Tequendama 1 provided the essential context for this paleogenomic investigation, allowing researchers to link ancient genetic data with a specific time, place, and cultural milieu.

Unveiling a Lost Lineage: A Paleogenomic Breakthrough

The reconstruction of such an ancient bacterial genome is a testament to the rapid advancements in paleogenomics, a field that specializes in extracting and analyzing DNA from ancient specimens. Ancient DNA (aDNA) is notoriously challenging to work with due to its highly degraded and fragmented nature, often contaminated by modern human or environmental microbial DNA. However, the sheer depth of sequencing performed in this study proved to be a critical factor.

Researchers were initially analyzing the human remains to study ancient human population history, generating an astonishing 1.5 billion fragments of genetic data – an exceptionally high volume for ancient DNA studies. It was during routine screening of this massive dataset that traces of Treponema pallidum DNA were independently detected by teams at the University of California, Santa Cruz, and the University of Lausanne. This serendipitous discovery underscored the power of comprehensive sequencing and advanced bioinformatics. Crucially, the depth of the data allowed the team to reconstruct a near-complete pathogen genome without the need for specialized "enrichment" techniques, which typically involve targeting and amplifying specific pathogen DNA sequences. This suggests that even subtle traces of ancient pathogens can be recovered from well-preserved remains with sufficient sequencing effort.

Upon reconstruction, the ancient DNA confirmed its identity as Treponema pallidum, the species responsible for modern treponemal diseases. However, the genetic analysis revealed a startling finding: this ancient genome did not precisely match any of the known Treponema pallidum subspecies that cause disease today. Instead, it represented a distinct, previously unknown lineage that branched off very early in the bacterium’s evolutionary history.

Tracing the Evolutionary Timeline of a Persistent Pathogen

Genetic analysis, employing sophisticated molecular clock models, allowed scientists to estimate the divergence times of this ancient strain. The data suggests that this newly discovered ancient T. pallidum lineage separated from other known T. pallidum lineages approximately 13,700 years ago. This timeline is particularly significant as it places the pathogen’s diversification firmly within the Late Pleistocene, a period coinciding with the initial waves of human migration into the Americas.

In stark contrast, the three modern subspecies of Treponema pallidum – T. pallidum subsp. pallidum (syphilis), T. pallidum subsp. pertenue (yaws), and T. pallidum subsp. endemicum (bejel) – appear to have diverged much later, around 6,000 years ago. This stark difference in divergence times highlights a much deeper and more complex evolutionary history for treponemal pathogens than previously understood. It suggests that these bacteria were not only present but also actively diversifying in the Americas thousands of years before the emergence of the modern forms of the diseases we recognize today.

Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU, commented on this complexity: "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." This emphasizes that the pathogen has an ancient history, even if the specific diseases as we know them might have emerged more recently.

The Treponemal Family: A Complex Spectrum of Disease

Treponema pallidum is a fascinating and medically important group of spiral-shaped bacteria, or spirochetes. While genetically nearly identical, their different subspecies cause distinct diseases with varying modes of transmission, geographical distributions, and clinical manifestations:

• Treponema pallidum subsp. pallidum: Responsible for venereal syphilis, a sexually transmitted infection that can progress through primary, secondary, latent, and tertiary stages, affecting multiple organ systems including the skin, nervous system, and cardiovascular system.
• Treponema pallidum subsp. pertenue: Causes yaws, a chronic skin-to-skin disease prevalent in warm, humid, tropical regions, particularly among children. It primarily affects the skin, bones, and joints, often resulting in disfiguring lesions. Yaws is typically transmitted through non-sexual skin contact.
• Treponema pallidum subsp. endemicum: Causes bejel, also known as endemic syphilis. This disease is found in arid, temperate regions and is transmitted non-sexually through direct contact, often within families or communities sharing eating utensils. Bejel primarily affects the skin, mucous membranes, and bones.
• Treponema carateum (or Treponema pallidum subsp. carateum): Causes pinta, a chronic skin disease characterized by discolored patches. Pinta is unique among treponemal diseases in that it is not known to affect internal organs or bones. It is endemic to Central and South America and is transmitted through direct skin-to-skin contact.

A significant aspect of this study is the speculation regarding the nature of the ancient lineage. Anna-Sapfo Malaspinas at the University of Lausanne and SIB Swiss Institute of Bioinformatics suggested, "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." While this remains a hypothesis, the geographical context and the early divergence of the ancient strain make it a compelling avenue for further investigation, potentially filling a crucial gap in our understanding of pinta’s evolutionary relationships and classification.

The challenges in disentangling the evolutionary paths of these diseases stem from their extreme genetic similarity coupled with their diverse clinical presentations and transmission routes. While skeletal remains can sometimes show signs of treponemal infections (e.g., periostitis, gummas), these markers are not always present or easily distinguishable between the different diseases. The ability to recover ancient DNA, even from bones without obvious lesions, as was the case here, offers a far more precise and powerful tool for unraveling this complex history.

The "Columbian Hypothesis" Revisited

This discovery holds profound implications for one of the most enduring debates in medical history: the origin of syphilis. The "Columbian Hypothesis" posits that syphilis was brought to Europe from the Americas by Columbus’s crew after 1492, rapidly spreading across the Old World. Evidence for this theory includes the sudden appearance and rapid spread of a virulent form of syphilis in Europe shortly after Columbus’s return, and archaeological evidence of treponemal diseases in pre-Columbian American remains.

Conversely, the "pre-Columbian hypothesis" suggests that treponemal diseases, including syphilis or its ancestors, were present in both the Old and New Worlds before 1492, possibly evolving into more virulent forms in the post-Columbian era. The current finding of a deeply divergent Treponema pallidum lineage in the Americas dating back 5,500 years lends substantial weight to the idea of a long and complex history of treponemal pathogens in the Americas, pre-dating any transatlantic contact. While it doesn’t definitively prove that venereal syphilis as we know it existed in the Americas prior to 1492, it demonstrates the ancient presence of its bacterial ancestor and highlights the region as a significant cradle for the evolution of this pathogen family. It implies a rich evolutionary tapestry of treponemal bacteria that co-existed with human populations in the Americas for millennia.

From Ancient Pathogens to Modern Public Health

The study’s implications extend far beyond historical curiosity. Understanding how infectious diseases emerged and diversified in the past is critical for anticipating how they might evolve in the future. As geneticist Lars Fehren-Schmitz from the University of California, Santa Cruz, noted, "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."

Pathogens like Treponema pallidum are constantly evolving, adapting to their human hosts and environmental pressures. By tracing the evolutionary pathways of ancient strains, scientists can gain insights into the genetic mechanisms that drive pathogenicity, host adaptation, and potentially even antibiotic resistance. This knowledge can inform modern public health strategies, helping societies better prepare for emerging infectious diseases, understand the dynamics of current epidemics, and develop more effective treatments and prevention methods. Davide Bozzi at the University of Lausanne and SIB Swiss Institute of Bioinformatics summarized this perspective, stating, "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."

Moreover, the success of recovering bacterial DNA from a tibia without visible signs of infection opens new avenues for paleopathological research. Previously, ancient pathogen studies often relied on samples from individuals exhibiting clear skeletal lesions. This discovery suggests that many more ancient human remains, even those appearing healthy, could harbor invaluable genetic information about past disease burdens, revolutionizing our understanding of ancient health and disease landscapes.

Ethical Engagement and International Collaboration

A crucial aspect of this groundbreaking research involved a robust commitment to ethical practices and community engagement. Before publishing their findings, the international research team actively shared their results with communities in Colombia. This process included consultations with local scholars, students, and Indigenous and non-Indigenous community members, as well as presentations and interviews with stakeholders. All required permits for the export and study of the remains were meticulously obtained.

Miguel Delgado emphasized the importance of this approach: "This process was essential because the findings are deeply connected to Colombia’s medical and cultural history. 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 respectful engagement sets a high standard for future paleogenomic studies, particularly those involving human remains with cultural significance.

The study represents a truly international and multidisciplinary collaborative effort. Key leadership was provided by Elizabeth Nelson, Davide Bozzi, Anna-Sapfo Malaspinas, Miguel Delgado, Lars Fehren-Schmitz, and Nasreen Broomandkhoshbacht (now at the University of Vermont). The broader team included experts from a diverse range of institutions, including 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 confluence of expertise in archaeology, molecular anthropology, paleopathology, genetics, and bioinformatics was essential to successfully navigate the complexities of this groundbreaking discovery, from the careful excavation of ancient remains to the intricate reconstruction and interpretation of a 5,500-year-old pathogen genome.