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Apart from the Black Death, there is not another historical disease that piques public interest quite like syphilis. The question of whether the bacterium responsible was brought to Europe from the New World following the voyage of Christopher Columbus, or whether it was already endemic in the Old World by that time, has been a source of debate for decades. In the last two years, however, several genomes of treponemal bacteria from pre-Columbian contexts in the Americas have been published, seemingly settling this age-old question and establishing syphilis as a New World disease. This is not the end of the story, however.
Over the last two decades, palaeopathological analyses have advanced dramatically, with scientists increasingly able to identify and sequence the DNA of various bacteria and viruses from the past. For a long time, however, syphilis (Treponema pallidum pallidum) – as well as the other three treponemal diseases of yaws (T pallidum pertenue), bejel (T pallidum endemicum), and pinta (T carateum) – remained elusive. In part, this reflects the pathophysiology of treponemal infections: skeletal involvement occurs in only a proportion of infected individuals and typically during later stages, when bacterial load in bone is low. As a result, even when paleopathologists identify lesions consistent with treponematosis, recovering pathogen DNA has proven challenging. As science has progressed, however, it became possible to extract small amounts of fragile pathogen DNA from a sample, and in 2018 the first archaeological examples of syphilis were identified and sequenced, finally opening the door to studying historical cases of syphilis (see ‘Science Notes’ in CA 342).
These genomes were from post-colonial contexts, and were therefore unable to address the disease’s origin – but a paper published in Nature in 2024 (https://doi.org/10.1038/s41586-024-08515-5) reported the first successful sequencing of genomes of T pallidum from pre-Contact contexts in the Americas. Based on reconstructions of the evolutionary history of these genomes, the researchers hypothesised that the most recent common ancestor for all four sub-species evolved around 9,000 years ago, after the date that people first populated the Americas.
More recent research published in Science (https://doi.org/10.1126/science.adw3020) has added another piece to the puzzle. The team behind this study identified a T pallidum genome almost by chance, as the skeleton that was analysed showed no signs of treponematosis visible to the naked eye. The bacteria were only found while conducting a broad metagenomic screening method that made possible the detection of various types of pathogen. The skeleton in question was found in the Tequendama I rock shelter in Sabana de Bogotá in Colombia (below), and was dated to c.5464-5309 years old. Genomic analysis seems to suggest that the reconstructed genome of ancient T pallidum (TE1-3) represents an early sister lineage of the modern subspecies. Using Bayesian molecular clock analyses, the team estimate that the divergence between TE1-3 and the common ancestor of all known T pallidum subspecies occurred around 13,700 years ago during the Late Pleistocene to Early Holocene. While this overlaps with the people of the Americas, the authors caution that this should be considered a lower-bound estimate due to reference bias and the low coverage of the ancient genome.

This discovery substantially extends the genomic record of T pallidum in the Americas by several millennia and strengthens evidence for a deep pre-Columbian presence of treponemal disease. At the same time, it complicates the picture. If a highly divergent lineage was circulating in South America 5,500 years ago, what other lineages might once have existed? And as for the great debate about syphilis, the authors encourage us to remember: the recovery of ancient Treponema pallidum genomes tells us about the evolutionary history of the pathogen and not the emergence of specific clinically defined diseases. Syphilis, yaws, bejel, and pinta are defined by their modes of transmission and clinical presentation, features that cannot be observed directly in archaeological remains and are not yet genetically distinguishable. As a result, the presence of T pallidum in the pre-Columbian Americas does not necessarily mean that syphilis, as a sexually transmitted disease, existed at that time.
Genomic data alone cannot determine when distinct disease syndromes took shape. These conditions are defined by transmission patterns, clinical presentation, and the demographics of affected individuals. Fully reconstructing their emergence will require the integration of palaeogenomic evidence with assessment of skeletal lesions and bioarchaeological context including demographic analysis of affected populations. Only by pairing pathogen genomes with evidence of how disease manifested in past communities can we begin to disentangle the evolutionary history of the bacterium from the history of the diseases it caused.
Text: Kathryn Krakowka / Image: Angélica Triana
