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

The groundbreaking discovery extends the known genetic history of Treponema pallidum by more than 3,000 years, pushing its documented presence in the Americas back millennia. The ancient genome, recovered from remains excavated at the Tequendama 1 rock shelter near present-day Bogotá, provides compelling evidence that treponemal diseases were circulating in the region far earlier than previously understood, fundamentally reshaping established timelines for these pervasive human pathogens.

A Glimpse into Deep Time: The Tequendama 1 Discovery

The human remains, meticulously unearthed from the Tequendama 1 site, date back approximately 5,500 years, placing them firmly within the Late Archaic period of South American prehistory. The Tequendama 1 rock shelter, located in the municipality of Soacha, Cundinamarca, southwest of Bogotá, is renowned for its archaeological significance, offering a window into the lives of early hunter-gatherer communities in the high-altitude Andean plains. Excavations at the site have previously yielded a wealth of artifacts and human remains, providing crucial insights into prehistoric human occupation, subsistence strategies, and cultural practices in the region. The individual from whom the Treponema pallidum genome was reconstructed was identified as a male, and surprisingly, his skeleton showed no visible pathological lesions typically associated with treponemal infections, such as those seen in advanced stages of syphilis or yaws. This absence of macroscopic evidence underscores the power of paleogenomics to reveal hidden aspects of ancient health, challenging assumptions based solely on osteological analysis.

"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, highlighting the transformative capacity of ancient DNA analysis in disease ecology.

Understanding Treponemal Diseases: A Modern Context

Treponema pallidum is a fascinating and formidable spiral-shaped bacterium, a spirochete, known for its ability to cause a suite of chronic, debilitating diseases collectively known as treponematoses. These diseases are characterized by their slow progression and wide range of symptoms affecting the skin, bones, and internal organs. Today, Treponema pallidum exists primarily in three closely related subspecies, each responsible for a distinct clinical syndrome:

• Treponema pallidum subsp. pallidum: This is the causative agent of syphilis, a sexually transmitted infection (STI) with global prevalence. Untreated, syphilis can progress through primary, secondary, latent, and tertiary stages, leading to severe neurological, cardiovascular, and musculoskeletal complications. Historically, syphilis has been a major public health challenge, with devastating social and demographic impacts.
• Treponema pallidum subsp. pertenue: This subspecies causes yaws, a chronic, disfiguring skin disease primarily affecting children in warm, humid, tropical regions. Yaws is typically transmitted through direct skin-to-skin contact. While not sexually transmitted, it shares significant genetic similarity with syphilis. The World Health Organization (WHO) has targeted yaws for eradication due to the effectiveness of single-dose oral azithromycin.
• Treponema pallidum subsp. endemicum: This subspecies is responsible for bejel (also known as endemic syphilis), a non-venereal treponematosis found predominantly in arid and semi-arid regions of Africa, the Middle East, and parts of Asia. Like yaws, bejel is transmitted through direct non-sexual contact, often within families or communities, and primarily affects children, causing lesions of the skin, mucous membranes, and bones.

A fourth treponemal disease, pinta, is caused by Treponema carateum or Treponema pallidum subsp. carateum. Pinta is characterized by disfiguring skin lesions but does not typically affect internal organs or bones. It is endemic to Central and South America. The lack of a complete genome for the pathogen responsible for pinta has long left a significant gap in our understanding of its evolutionary relationships and precise classification, a gap that this new Colombian discovery might begin to address.

Despite their nearly identical genetic makeup—often sharing over 99.8% sequence identity—scientists still grapple with the precise evolutionary pathways and environmental factors that led to the divergence of these distinct disease forms. While skeletal remains can sometimes bear tell-tale signs of infection, providing macroscopic evidence of treponemal disease in ancient populations, genetics often reveal a more intricate and nuanced narrative. Large gaps have historically persisted between what paleopathological observations on bones can suggest and what ancient DNA can definitively confirm about disease evolution and epidemiology.

A Serendipitous Breakthrough in Paleogenomics

The reconstruction of this 5,500-year-old Treponema pallidum genome represents a significant triumph for the field of paleogenomics, which involves the study of ancient DNA to understand evolutionary processes and past life forms. The discovery itself was somewhat unexpected. Researchers at the University of California, Santa Cruz, and the University of Lausanne, along with the SIB Swiss Institute of Bioinformatics, were initially sequencing the ancient individual’s DNA from the Tequendama 1 site to investigate ancient human population history in the Americas. This ambitious project generated an astounding 1.5 billion fragments of genetic data—a volume far exceeding typical yields for ancient human remains.

During routine bioinformatics screening of this massive dataset, teams working independently at Santa Cruz and Lausanne simultaneously and serendipitously detected minute traces of Treponema pallidum DNA. Recognizing the immense potential of this finding, they swiftly combined their efforts to investigate further. The sheer depth of the sequencing data proved to be a critical factor. Even though bacterial DNA constituted only a minuscule fraction of the total genetic material recovered, the extensive coverage allowed the researchers to reconstruct a high-quality, near-complete pathogen genome without the need for specialized enrichment techniques, which are often employed to increase the proportion of target DNA in a sample.

Crucially, the researchers sampled a tibia, or shin bone, from the individual. Tibiae are not typically the primary choice for ancient DNA studies, with teeth and petrous bones (part of the temporal bone in the skull) generally yielding higher quantities and better preservation of endogenous DNA. The success of recovering a pathogen genome from a tibia, especially one without visible signs of disease, broadens the scope of future paleogenomic investigations, suggesting that a wider range of skeletal elements may harbor valuable genetic information about ancient infections. This methodological breakthrough could open new avenues for studying the history of disease in contexts where traditionally preferred samples are unavailable or yield poor results.

An Ancient Lineage: Rewriting the Treponemal Timeline

The detailed genetic analysis confirmed that the ancient DNA belonged unequivocally to the species Treponema pallidum. However, to the astonishment of the research team, this ancient genome did not perfectly match any of the known modern subspecies that cause syphilis, yaws, or bejel today. While closely related to contemporary strains, the ancient genome represented a distinct lineage that had diverged very early in the bacterium’s evolutionary history.

"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 added, "At this time, we cannot prove this is the case, but it is a lead worth investigating further." This hypothesis is particularly intriguing given pinta’s historical presence and skin-specific manifestations, which might explain the lack of skeletal lesions in the Tequendama 1 individual.

Based on advanced phylogenetic analyses, scientists estimate that this ancient Colombian strain separated from other T. pallidum lineages approximately 13,700 years ago. This dating places its divergence deep into the Late Pleistocene or early Holocene, a period coinciding with major human migrations across the Bering land bridge into the Americas. 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 provide critical insights into the deep evolutionary history of Treponema pallidum, supporting earlier research suggesting a long and diverse history of treponemal pathogens in the distant past, predating the rise of complex urban societies.

"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," clarified Elizabeth Nelson, a molecular anthropologist and paleopathologist at SMU. This statement points to the ongoing "Columbian Exchange" debate, which postulates that syphilis was introduced to Europe from the Americas by Columbus’s crew, or alternatively, that it was an Old World disease that merely mutated into a more virulent form upon contact with New World populations. While this new genome doesn’t definitively settle that origin, it firmly establishes a much deeper indigenous presence of Treponema pallidum in the Americas, pushing the timeline of diversification significantly backward.

A Genetic Puzzle with Profound Implications

Tracing the precise origins and evolutionary trajectories of treponemal diseases has always been exceptionally challenging due to the bacteria’s extreme genetic similarity. Despite their near-identical genomes, these pathogens spread through different routes (sexual, non-sexual skin contact) and can manifest in remarkably varied clinical syndromes, making their evolutionary paths notoriously difficult to untangle. This genetic uniformity, coupled with diverse clinical outcomes, underscores the subtle genetic changes that can drive significant shifts in pathogenicity and transmission.

"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 extended timeline implies that Treponema pallidum may have co-evolved with early human populations during their initial dispersal across the continents, possibly even accompanying the first waves of migration into the Americas. Such a deep co-evolutionary history suggests a long-standing host-pathogen relationship, where humans and Treponema pallidum have influenced each other’s genetic and immunological adaptations over millennia.

The discovery builds upon years of dedicated 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 provided invaluable detailed background on the skeletal remains themselves, laying the groundwork for this advanced genetic analysis. This multidisciplinary approach, combining traditional archaeology with cutting-edge paleogenomics, exemplifies the future of reconstructing ancient disease landscapes.

Why Ancient Disease History Matters Today: Preparing for Future Health Threats

The study of ancient diseases, or paleopathology and paleogenomics, is far more than an academic exercise in historical reconstruction. By meticulously unraveling how infectious diseases emerged, evolved, and changed their virulence and transmission patterns in the distant past, scientists gain critical insights into the fundamental mechanisms of host-pathogen co-evolution. This knowledge is invaluable for anticipating how pathogens might adapt and spread in the future. Understanding the genetic plasticity of bacteria like Treponema pallidum over millennia can inform public health strategies, helping modern societies better prepare for potential emerging infectious diseases or the re-emergence of old ones. It highlights the dynamic nature of pathogens and the continuous arms race between microbial invaders and human immune systems.

Before publishing their groundbreaking results, the research team made a conscious and commendable effort to share their findings with local communities and scholars in Colombia. Recognizing the profound significance of this discovery to the country’s medical and cultural history, they consulted with local academics, students, and Indigenous and non-Indigenous community members. This engagement included presentations and interviews, ensuring a collaborative and ethically responsible approach to disseminating sensitive scientific information. 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," articulated 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 sets a vital precedent for future paleogenomic research, emphasizing the importance of respecting cultural heritage and fostering collaborative relationships with source communities.

An International Collaboration of Expertise

The success of this complex interdisciplinary study is a testament to the power of international scientific collaboration. In addition to Elizabeth Nelson, Davide Bozzi, Anna-Sapfo Malaspinas, Miguel Delgado, and Lars Fehren-Schmitz, the research was notably co-led by Nasreen Broomandkhoshbacht, now at the University of Vermont.

The broader international team comprised a diverse array of specialists, including Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a leading figure in bioarchaeology; Carlos Eduardo G. Amorim of California State University, Northridge; Melissa Estrada Pratt of the Instituto Colombiano de Antropología e Historia in Bogotá, Colombia, ensuring critical local expertise; Gilbert Greub of the University of Lausanne and Lausanne University Hospital in Switzerland, contributing microbiology and infectious disease knowledge; Nicolas Rascovan of the Institut Pasteur in Paris, an expert in ancient pathogen genomics; and David Šmajs of Masaryk University in the Czech Republic, a prominent researcher in Treponema pallidum genetics. This confluence of expertise across genetics, anthropology, archaeology, microbiology, and bioinformatics was essential in navigating the intricate challenges of recovering, analyzing, and interpreting such ancient and delicate genetic material.

This remarkable discovery not only pushes back the known timeline of Treponema pallidum in the Americas by several millennia but also opens new avenues for understanding the complex evolutionary history of human pathogens. It reinforces the critical role of paleogenomics in illuminating our past, providing crucial context for the diseases that continue to shape human health in the present, and potentially guiding our preparedness for the health challenges of the future. The ancient genome from Tequendama 1 stands as a powerful reminder that the story of human health is inextricably linked to the deep history of our microbial companions.