Researchers have achieved a remarkable feat by reconstructing the complete genome of Treponema pallidum from human skeletal remains approximately 5,500 years old, unearthed in the Sabana de Bogotá area of Colombia. This spiral-shaped bacterium is the culprit behind several severe infectious conditions in contemporary times, most notably syphilis. The groundbreaking results, detailed in the prestigious journal Science, dramatically broaden the scientific community’s understanding of the longstanding presence of these pathogens in human societies.
The skeletal remains originated from a rock shelter in the vicinity of modern-day Bogotá, with radiocarbon dating placing them around 5,500 years in the past. Through the identification of this prehistoric genome, scientists have pushed back the documented genetic timeline of Treponema pallidum by over 3,000 years. This discovery lends substantial credibility to the hypothesis that treponemal infections were prevalent across the Americas much earlier than historical records or prior evidence had indicated.
“Our research demonstrates the extraordinary capabilities of paleogenomics in illuminating the evolutionary trajectories of species and the associated health hazards faced by ancient and modern populations alike,” explained Lars Fehren-Schmitz, a geneticist based at the University of California, Santa Cruz.
What Constitutes Treponemal Diseases?
Treponema pallidum represents a distinctive spiral bacterium that manifests today in three closely related subspecies, each responsible for a distinct illness: syphilis, yaws, and bejel. An additional treponemal condition, known as pinta, stems from Treponema carateum or the subspecies Treponema pallidum subsp. carateum. To date, no full genome from the pinta-causing agent has been isolated, fostering ongoing uncertainties regarding its phylogenetic connections and proper taxonomic placement.
Even though these subspecies share virtually indistinguishable genetic profiles, the precise timing and mechanisms behind the emergence of their varied disease manifestations remain elusive. While pathological alterations on skeletal elements can occasionally signal infection, genomic data frequently unveils a far more intricate narrative. Substantial discrepancies persist between the insights gleaned from osteological evidence and those verified through ancient DNA analyses concerning the development of these diseases over time.
Discovery of an Extinct Branch in a Well-Known Pathogen
In the course of this investigation, the research team verified that the ancient DNA sequence aligned with the Treponema pallidum species, yet it diverged notably from all currently recognized disease-causing variants. Though it exhibits close kinship to present-day strains, this archaic genome branched off at a very early juncture in the bacterium’s phylogenetic tree.
“It’s conceivable that we’ve identified a primordial variant of the pinta pathogen, about which our knowledge is limited, but which is acknowledged as endemic from Central to South America and primarily affects the skin with localized symptoms,” noted Anna-Sapfo Malaspinas, affiliated with the University of Lausanne and serving as group leader at the SIB Swiss Institute of Bioinformatics. “While we lack definitive proof at this stage, this represents a promising avenue for future exploration.”
Genetic evaluations indicate that this ancient strain diverged from fellow T. pallidum lineages approximately 13,700 years ago. By comparison, the trio of extant subspecies emerged far more recently, roughly 6,000 years in the past. These chronological estimates corroborate preceding studies and underscore the remarkable diversity of treponemal bacteria in remote epochs.
“The genomic data available today, including the one we’ve sequenced, fails to settle the enduring controversy over the geographic origins of these specific disease syndromes, but it unequivocally illustrates a protracted evolutionary chronicle of treponemal pathogens that were already undergoing diversification in the Americas millennia before what was previously recognized,” stated Elizabeth Nelson, a molecular anthropologist and paleopathologist at Southern Methodist University.
Unraveling a Genetic Enigma with Relevance to Contemporary Health
Delving into the roots of treponemal diseases presents formidable obstacles due to the pathogens’ near-genetic uniformity. Paradoxically, they propagate via disparate transmission routes and elicit markedly varied clinical presentations, complicating efforts to disentangle their developmental histories.
“These findings extend the human association with T. pallidum back by thousands of years—potentially exceeding 10,000 years into the Late Pleistocene epoch,” remarked Davide Bozzi, a researcher at the University of Lausanne and the SIB Swiss Institute of Bioinformatics.
This revelation stems from extensive archaeological and genetic endeavors at the Tequendama 1 locality. Prior investigations conducted by archaeologist Miguel Delgado from the Universidad Nacional de La Plata in Argentina, alongside Fehren-Schmitz, furnished critical contextual details about the individual skeleton.
Serendipitous Detection Amid Vast DNA Datasets
The identification of the pathogen was entirely fortuitous rather than a targeted pursuit. The team initially sequenced the person’s DNA to probe ancient human demographic patterns, generating an impressive 1.5 billion genetic fragments—substantially exceeding standard volumes. In the midst of standard quality control protocols, separate groups at the University of California, Santa Cruz, and the University of Lausanne each spotted indications of T. pallidum and opted to collaborate on deeper analysis.
Despite comprising merely a minuscule fraction of the overall genetic content, the comprehensive sequencing coverage empowered the scientists to assemble the bacterium’s full genome sans the need for bespoke amplification methods.
The ailments induced by T. pallidum—namely bejel, yaws, and syphilis—may imprint detectable lesions on osseous tissues, albeit selectively and not universally among sufferers. Historically, most ancient bacterial genomes of this type have been extracted from dental or skeletal materials exhibiting overt pathological signs. Here, however, the skeleton bore no apparent infection indicators. The researchers opted for a tibia, or lower leg bone, an unconventional choice for paleogenomic extraction. This methodological triumph implies that even unremarkable bones can harbor crucial microbial genetic legacies.
The Enduring Significance of Historical Disease Patterns
Comprehending the genesis and transformation of infectious agents through history equips scientists to forecast their prospective adaptations. Such foresight is invaluable for equipping today’s populations against emerging epidemiological challenges.
Prior to dissemination, the investigators disseminated preliminary outcomes to Colombian stakeholders, acknowledging the profound ties to national medical heritage. They interfaced with regional academics, students, and residents via workshops, presentations, and dialogues. All requisite authorizations for material transport and analysis were duly secured.
“This collaborative engagement was indispensable, given the intimate links between our discoveries and Colombia’s medical and cultural narratives,” emphasized Delgado. “Involving academics, learners, and both Indigenous and non-Indigenous locals fosters ethical dissemination and contextualization in tandem with those communities. It cultivates mutual confidence, promotes judicious handling of delicate findings, and affirms community sovereignty over their heritage.”
A Global Team Effort
Complementing the efforts of Nelson, Bozzi, Malaspinas, Delgado, and Fehren-Schmitz, the project was co-directed by Nasreen Broomandkhoshbacht, currently at the University of Vermont. The extensive consortium further encompassed Kalina Kassadjikova from the University of California, Santa Cruz; Jane Buikstra of Arizona State University; Carlos Eduardo G. Amorim from California State University, Northridge; Melissa Estrada Pratt affiliated with 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 from the Institut Pasteur in Paris; and David Šmajs of Masaryk University in the Czech Republic.
