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

Scientists have successfully reconstructed the genome of Treponema pallidum, the bacterium responsible for serious infectious diseases like syphilis, from human remains dating back approximately 5,500 years. Unearthed in the Sabana de Bogotá region of Colombia, this groundbreaking discovery, detailed in the journal Science, dramatically extends the documented genetic history of these infections in human populations by more than 3,000 years, offering unprecedented insights into their ancient origins and evolution.

The Colombian Discovery: Rewriting Disease Timelines

The ancient human remains were excavated from a rock shelter site, known as Tequendama 1, situated near present-day Bogotá. The identification of this remarkably preserved Treponema pallidum genome pushes back the known genetic timeline of treponemal diseases by several millennia, providing compelling evidence that these pathogens circulated in the Americas far earlier than previously understood. This finding has profound implications for understanding human health in antiquity and the deep evolutionary relationships between humans and their microbial inhabitants.

Lars Fehren-Schmitz, a geneticist at the University of California, Santa Cruz, and a co-author of the study, emphasized the significance of this methodology. "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," he stated, underscoring the power of ancient DNA analysis to unravel complex biological histories. The ability to recover such ancient and intact genetic material from a pathogen that often leaves ambiguous skeletal traces represents a major leap forward in paleomicrobiology.

Unearthing Ancient Pathogens: The Tequendama 1 Site

The Tequendama 1 rock shelter has long been a site of significant archaeological interest, yielding crucial information about early human occupation in the Americas. Previous work by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina, in collaboration with Fehren-Schmitz, provided detailed context for the human skeleton from which the ancient Treponema pallidum genome was retrieved. The individual, whose remains date to the mid-Holocene period, offers a unique window into the health landscape of pre-Columbian South America.

Remarkably, the skeleton itself showed no visible evidence of infection, a common challenge in paleopathological studies of treponemal diseases. These infections can leave marks on bones, but only under specific conditions and not consistently across all infected individuals. The research team sampled a tibia, or shin bone, which is not typically the primary choice for ancient DNA studies targeting pathogens. The success of this approach demonstrates that even bones without overt disease markers can harbor invaluable genetic information, opening new avenues for future investigations.

The discovery of the pathogen was, in fact, an unexpected find. Researchers initially embarked on a project to sequence the individual’s DNA to study ancient human population history in the region. This ambitious undertaking generated approximately 1.5 billion fragments of genetic data, an exceptionally high volume compared to typical ancient DNA sequencing efforts. During routine screening of this massive dataset, independent teams at the University of California, Santa Cruz, and the University of Lausanne serendipitously detected traces of T. pallidum. This independent verification by two separate laboratories further strengthens the credibility and robustness of the findings. Crucially, the sheer depth of sequencing allowed the researchers to reconstruct the pathogen’s complete genome without needing specialized enrichment techniques typically employed to isolate microbial DNA from host material, a testament to the quality of the ancient DNA preservation.

Understanding Treponemal Diseases: A Family of Complex Pathogens

Treponema pallidum is a fascinating spiral-shaped bacterium, or spirochete, known for its highly invasive nature and its ability to cause a spectrum of chronic, debilitating diseases. Today, it exists primarily in three closely related subspecies, each responsible for a distinct clinical syndrome:

• Treponema pallidum subsp. pallidum: Causes syphilis, a sexually transmitted infection that, if untreated, can progress through primary, secondary, latent, and tertiary stages, affecting various organ systems, including the skin, mucous membranes, central nervous system, and cardiovascular system. It is globally prevalent.
• Treponema pallidum subsp. pertenue: Causes yaws, a chronic skin infection primarily affecting children in tropical and subtropical regions. It is typically transmitted through direct skin-to-skin contact and can lead to disfiguring lesions on the skin, bones, and joints. The World Health Organization (WHO) has targeted yaws for eradication.
• Treponema pallidum subsp. endemicum: Causes bejel (also known as endemic syphilis), a non-sexually transmitted disease found mainly in arid regions of Africa and the Middle East. Transmission typically occurs through direct oral contact, often among children sharing eating utensils. Symptoms include skin lesions, oral ulcers, and bone involvement.

A fourth treponemal disease, pinta, is caused by Treponema carateum or sometimes classified as Treponema pallidum subsp. carateum. Pinta is characterized by skin lesions that change color over time, primarily affecting the skin and not typically involving internal organs. It is endemic to Central and South America and is spread through non-sexual skin-to-skin contact. The 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 taxonomic classification.

Despite their nearly identical genetic makeup—often differing by less than 0.2% at the genomic level—scientists still grapple with understanding precisely when and how these different disease forms emerged and diverged, given their distinct modes of transmission and clinical presentations. While skeletal remains can sometimes show pathological signs indicative of treponemal infections, the nuanced genetic differences often tell a more complex story, highlighting the crucial role of ancient DNA in bridging the gaps between paleopathological observations and the precise evolutionary trajectories of these pathogens.

A Deep Evolutionary Root: The "Lost Lineage" and Its Significance

A particularly striking finding of this study is that the ancient Treponema pallidum DNA, while unequivocally belonging to the species, does not precisely match any of the known modern forms that cause disease today. Instead, the ancient genome represents a distinct "lost lineage," closely related to modern strains but having diverged very early in the bacterium’s evolutionary history.

Anna-Sapfo Malaspinas, at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics, offered a compelling hypothesis regarding 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," she suggested. "At this time, we cannot prove this is the case, but it is a lead worth investigating further." This inference is particularly intriguing given pinta’s geographical distribution and its generally skin-localized manifestations, which might explain the absence of significant skeletal markers in the Tequendama 1 individual.

Based on detailed genetic analysis, the research team estimates that this ancient Colombian strain separated from other T. pallidum lineages approximately 13,700 years ago. 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 updated timelines provide critical support for earlier research indicating a deep and diverse evolutionary history for treponemal pathogens, extending far into the distant past. Davide Bozzi, a researcher at the University of Lausanne and SIB Swiss Institute of Bioinformatics, elaborated on this, 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." This significantly rewrites the narrative of human-pathogen co-evolution.

Challenging Historical Narratives: The Pre-Columbian Debate

The discovery from Tequendama 1 directly impacts a long-standing and often contentious debate in medical history: the origin of syphilis. Traditionally, two main theories have dominated:

1. The Columbian Theory (or "New World" Theory): This theory posits that syphilis originated in the Americas and was brought to Europe by Christopher Columbus’s returning sailors in the late 15th century, leading to a devastating epidemic across the Old World.
2. The Unitarian Theory (or "Old World" Theory): This theory suggests that treponemal diseases, including syphilis, yaws, and bejel, were ancient and widely distributed across both the Old and New Worlds long before Columbus. Proponents argue that the different clinical manifestations observed today are simply variations of a single pathogen, adapted to different environmental and social conditions over millennia.

Prior to this discovery, skeletal evidence for pre-Columbian treponemal diseases in the Americas was sporadic and often debated, while genetic evidence was almost nonexistent for such ancient periods. The 5,500-year-old T. pallidum genome from Colombia provides concrete genetic proof that treponemal pathogens were present and diversifying in the Americas thousands of years before the arrival of Europeans. While the findings do not definitively resolve the debate about the specific origin of venereal syphilis itself—as this ancient strain is distinct from modern syphilis—they strongly bolster the argument for an ancient and diverse presence of treponemal diseases in the Americas.

Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU, articulated this nuance: "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 evidence shifts the focus from a singular origin point to a more complex, multi-regional evolutionary narrative for the broader family of treponemal bacteria.

The Power of Paleogenomics: Unseen Insights from Ancient Bones

Tracing the origins and evolutionary paths of treponemal diseases has always been a formidable challenge due to the bacteria’s extreme genetic similarity across subspecies, coupled with their vastly different modes of transmission and diverse clinical outcomes. The ability of paleogenomics to bypass the limitations of macroscopic paleopathology—where disease signs on bones can be absent or ambiguous—is revolutionizing our understanding.

The fact that this ancient T. pallidum genome was successfully reconstructed from a tibia of an individual showing no visible skeletal evidence of infection is a significant methodological triumph. Most ancient genomes of this bacterium recovered to date have come from teeth or bones that clearly exhibited signs of disease. This study demonstrates that even seemingly unaffected skeletal elements can harbor crucial genetic information, greatly expanding the potential scope for future paleogenomic investigations into infectious diseases. This underscores the importance of thorough and systematic ancient DNA screening, even when archaeological evidence does not immediately suggest pathogen presence.

Implications for Modern Medicine and Public Health

The study’s findings extend beyond academic interest, carrying significant implications for modern medicine and public health. By meticulously tracing how infectious diseases emerged, evolved, and adapted over millennia, scientists gain invaluable insights into the fundamental principles of pathogen evolution. This historical perspective can help anticipate how contemporary pathogens might change in the future, informing strategies for disease surveillance, prevention, and treatment.

Understanding the deep evolutionary history of Treponema pallidum, for instance, could shed light on factors that drive shifts in virulence, transmission routes, or host specificity. Such knowledge is crucial for developing more effective vaccines, diagnostic tools, and therapeutic interventions for diseases that continue to pose global health challenges today. The study also highlights the dynamic nature of pathogen-host interactions and the potential for ancient lineages to provide clues about mechanisms of persistence and adaptation that are still relevant.

Ethical Research: Engaging Local Communities

Beyond the scientific revelations, the research team demonstrated a commitment to ethical and responsible scholarship, particularly in light of the discovery’s profound connection to Colombia’s medical and cultural heritage. Before publishing their findings, the researchers actively shared their results with communities in Colombia. This involved consulting local scholars, students, and Indigenous and non-Indigenous community members through presentations and interviews, fostering a collaborative dialogue with stakeholders. All necessary permits for the export and study of the human remains were obtained, adhering to international and national regulations.

Miguel Delgado, a key figure in the archaeological work at Tequendama 1, emphasized the critical importance of this community engagement. "This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," Delgado stated. "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 model of integrated research, combining cutting-edge science with community partnership, serves as an exemplar for future studies involving ancient human remains and their cultural contexts.

An International Effort in Scientific Discovery

This landmark research was the result of a truly international and interdisciplinary collaboration, bringing together expertise from diverse fields including genetics, anthropology, paleopathology, and bioinformatics. In addition to Elizabeth Nelson, Davide Bozzi, Anna-Sapfo Malaspinas, Miguel Delgado, and Lars Fehren-Schmitz, the study was co-led by Nasreen Broomandkhoshbacht, now at the University of Vermont.

The broader research 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 collective effort underscores the global nature of scientific inquiry and the necessity of pooling diverse skills and perspectives to tackle complex questions about human history and health. The discovery of this ancient Treponema pallidum genome not only rewrites chapters of medical history but also sets a new standard for the integration of scientific rigor, ethical practice, and community engagement in paleogenomic research.