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

A Landmark Discovery in Paleogenomics

The ancient human remains, excavated from a rock shelter near present-day Bogotá, date back roughly 5,500 years. The successful recovery and sequencing of a complete Treponema pallidum genome from these remains represent a monumental achievement in the field of paleogenomics. This unprecedented genetic window into the past reveals a previously unknown lineage of the bacterium, distinct from any modern strains, yet closely related to the Treponema pallidum species that causes syphilis, yaws, and bejel today. The study’s lead authors, an international team of geneticists, anthropologists, and paleopathologists, highlight the profound implications of this finding for understanding human-pathogen co-evolution and the deep history of infectious diseases.

"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 at the University of California, Santa Cruz, underscoring the power of ancient DNA analysis to unravel long-standing biological mysteries. This particular excavation at the Tequendama 1 site, renowned for its rich archaeological record, has now yielded insights far beyond initial expectations.

Understanding Treponemal Diseases: A Complex Family

Treponema pallidum is a genus of spiral-shaped bacteria, known as spirochetes, notorious for causing a group of infectious diseases collectively known as treponematoses. These diseases manifest in various forms, primarily due to three closely related subspecies of Treponema pallidum, each responsible for a distinct clinical syndrome:

• Treponema pallidum subspecies pallidum: This is the causative agent of syphilis, a sexually transmitted infection that, if left untreated, can progress through primary, secondary, latent, and tertiary stages, affecting multiple organ systems including the brain, heart, and bones.
• Treponema pallidum subspecies pertenue: This subspecies causes yaws, a chronic, disfiguring skin infection primarily affecting children in tropical and subtropical regions. It is typically transmitted through direct skin contact.
• Treponema pallidum subspecies endemicum: This bacterium is responsible for bejel (also known as endemic syphilis), a non-sexually transmitted treponematosis found predominantly in arid regions, spread through direct skin-to-skin contact or shared eating utensils.

A fourth treponemal disease, pinta, is caused by Treponema carateum or, alternatively, Treponema pallidum subspecies carateum. Pinta primarily affects the skin, causing disfiguring lesions, and is prevalent in Central and South America. Intriguingly, no complete genome of the pathogen responsible for pinta has yet been recovered, leaving significant gaps in our understanding of its evolutionary relationships and precise classification within the treponemal family.

Despite their nearly identical genetic makeup—often differing by less than 0.2% at the nucleotide level—scientists still grapple with the exact timeline and mechanisms by which these different disease forms emerged and diverged. While skeletal remains can sometimes exhibit pathological signs of infection, such as periosteal reactions or gummatous lesions indicative of chronic treponemal disease, ancient genetics often tells a more nuanced and complex story. Large gaps have historically remained between what physical bone pathologies can reveal and what ancient DNA analysis can definitively confirm about the evolution and antiquity of these elusive pathogens.

A Lost Lineage: An Evolutionary Puzzle

In this groundbreaking study, researchers confirmed that the ancient DNA recovered from the Colombian remains indeed belonged to the species Treponema pallidum. However, phylogenetic analysis revealed a startling finding: this ancient genome did not precisely match any of the known modern forms that cause disease today. Although closely related to contemporary strains, the ancient genome represents a distinct lineage that appears to have split off very early in the bacterium’s evolutionary history. This discovery adds a crucial branch to the Treponema pallidum phylogenetic tree.

"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," suggested Anna-Sapfo Malaspinas at the University of Lausanne and group leader at the SIB Swiss Institute of Bioinformatics. "At this time, we cannot prove this is the case, but it is a lead worth investigating further." The geographical context of the find—Colombia—lends credibility to this hypothesis, given pinta’s historical prevalence in the region.

Based on detailed genetic analysis, scientists estimate that this ancient strain separated from other T. pallidum lineages approximately 13,700 years ago. In stark contrast, the three modern subspecies (causing syphilis, yaws, and bejel) appear to have diverged much more recently, around 6,000 years ago. These revised timelines provide critical support for earlier research suggesting a much deeper and more diverse evolutionary history for treponemal pathogens in the distant past than previously assumed. This extended timeline also places the origin of these pathogens within the Late Pleistocene or early Holocene, a period of significant human migration and environmental change in the Americas.

"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 finding fundamentally alters our understanding of the antiquity of treponemal infections in the New World, pushing back their known presence by millennia.

The "Columbian Exchange" Debate Revisited

For centuries, the origin of syphilis has been a subject of intense scientific and historical debate. The prevailing "Columbian Exchange" hypothesis posits that syphilis was a New World disease, brought back to Europe by Christopher Columbus’s crew after their voyages to the Americas in the late 15th century. This theory is supported by the sudden emergence and rapid spread of a severe syphilis epidemic in Europe shortly after 1492, as well as archaeological evidence of treponemal disease in pre-Columbian American skeletons.

However, alternative theories suggest that treponemal diseases might have existed in the Old World prior to Columbus, or that a less virulent form of Treponema pallidum was already present in Europe, which then evolved into the more virulent syphilis strain after contact with New World populations. The discovery of a 5,500-year-old Treponema pallidum genome in South America adds significant weight to the argument for an ancient American origin of these pathogens. While it does not definitively "resolve" the Columbian Exchange debate in its entirety, it certainly complicates any simplistic narrative of Old World purity before 1492. It strongly suggests that diverse treponemal strains were indigenous to the Americas for millennia, evolving alongside early human populations. The ancient Colombian strain’s deep divergence further supports the idea that the Americas were a hotbed of treponemal evolution long before trans-Atlantic contact.

Paleogenomics: An Unexpected Find in Massive DNA Data

Tracing the origins of treponemal diseases has always been especially challenging due to the bacteria’s extreme genetic similarity across its various forms, coupled with their diverse modes of transmission and often vastly different clinical manifestations. This genetic subtlety has made untangling their evolutionary paths a formidable task.

"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," asserted researcher Davide Bozzi at the University of Lausanne and SIB Swiss Institute of Bioinformatics. This timeframe aligns with early human migrations into the Americas, suggesting a long co-evolutionary history between humans and these pathogens since the earliest peopling of the continent.

The discovery itself was serendipitous. The pathogen was not initially the target of the research. Scientists had originally sequenced 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 projects. During routine screening of this vast dataset, teams at the University of California, Santa Cruz, and the University of Lausanne independently detected minute traces of T. pallidum DNA. Recognizing the potential significance, they decided to collaborate and investigate further.

Despite bacterial DNA constituting only a tiny fraction of the total genetic material, the sheer depth of sequencing allowed the team to reconstruct a near-complete genome of the pathogen. This was achieved without resorting to specialized enrichment techniques, which are often necessary to isolate pathogen DNA from overwhelming amounts of human and environmental DNA. This methodological success demonstrates the increasing power of high-throughput sequencing and advanced bioinformatics in paleogenomics.

Moreover, the human skeleton itself showed no visible evidence of infection—a crucial detail. Most ancient genomes of Treponema pallidum have previously been recovered from teeth or bones that clearly exhibited macroscopic signs of disease. In this case, researchers sampled a tibia, or shin bone, which is not commonly prioritized for ancient DNA studies, especially when no lesions are apparent. The success of this approach suggests that even bones without obvious disease markers can preserve invaluable genetic information, opening new avenues for future paleopathological investigations and potentially expanding the pool of suitable ancient human remains for disease discovery.

The Tequendama 1 Site: A Window into Ancient Colombia

The discovery builds on decades of archaeological and genetic work at the Tequendama 1 site, located in the Sabana de Bogotá, a high-altitude plateau in the Colombian Andes. This rock shelter has been a crucial archaeological locus for understanding early human occupation in South America. Earlier studies by archaeologist Miguel Delgado of the Universidad Nacional de La Plata in Argentina, in collaboration with Fehren-Schmitz, had provided detailed background on the specific human skeleton from which the Treponema pallidum genome was retrieved. The site has yielded evidence of continuous human occupation spanning from the Late Pleistocene through the Holocene, offering a unique chronological sequence for studying ancient human adaptations, subsistence strategies, and now, disease history. The context of this well-preserved site was instrumental in providing the robust chronological framework necessary for validating the ancient DNA findings.

Why Ancient Disease History Matters Today

The study of ancient diseases, or paleopathology, is far more than an academic exercise; it carries profound implications for modern public health. By learning how infectious diseases emerged, evolved, and changed their virulence and transmission patterns in the distant past, scientists hope to better anticipate how current and future pathogens might behave. This knowledge is critical for informing strategies to prepare for potential health threats, including the emergence of new diseases or the re-emergence of old ones, and for developing more effective treatments and vaccines.

Understanding the deep evolutionary roots of Treponema pallidum provides a crucial baseline for studying its remarkable adaptability. The fact that a lineage diverged 13,700 years ago, and modern forms around 6,000 years ago, illustrates the dynamic nature of pathogen evolution. This historical perspective can help scientists model how genetic changes in bacteria correlate with shifts in disease manifestation, host adaptation, and geographic spread, offering valuable insights into current epidemics and future pandemic preparedness.

Ethical Considerations and Community Engagement

Before publishing their groundbreaking results, the research team undertook a vital step: they shared their findings with communities in Colombia, recognizing the discovery’s profound importance to the country’s medical and cultural history. This involved extensive consultation with local scholars, students, and community members, as well as engagement with stakeholders through presentations and interviews. All required permits for the export and study of the human remains were meticulously obtained and adhered to.

"This process was essential because the findings are deeply connected to Colombia’s medical and cultural history," emphasized 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 ethical research and community engagement sets a high standard for paleogenomic studies, particularly those involving human remains and ancient disease.

An International Collaboration

The successful reconstruction of this ancient Treponema pallidum genome was the result of an extensive international collaboration, bringing together expertise from diverse scientific disciplines and geographical locations. 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 team included Kalina Kassadjikova of the University of California, Santa Cruz; Jane Buikstra of Arizona State University, a leading paleopathologist; Carlos Eduardo G. Amorim of California State University, Northridge; Melissa Estrada Pratt of the Instituto Colombiano de Antropología e Historia in Bogotá, Colombia, ensuring local expertise; Gilbert Greub of the University of Lausanne and Lausanne University Hospital in Switzerland; Nicolas Rascovan of the Institut Pasteur in Paris, a specialist in ancient pathogen genomics; and David Šmajs of Masaryk University in the Czech Republic, an expert on Treponema pallidum genomics. This multinational, multidisciplinary effort underscores the complex nature of paleogenomic research and the collaborative spirit required to unlock the secrets of humanity’s ancient past and its enduring relationship with disease.