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Ancient Treponema Genomes Suggest Path for Refining Syphilis, Yaws Origins

NEW YORK (GenomeWeb) – A new genomic analysis of ancient Treponema pallidum samples suggests that genetic analyses can be used to distinguish between the sub-species causing syphilis and yaws — conditions that often mar human skeletal remains with similar lesions.

"Our work demonstrates the value of molecular identification of ancient pathogens, particularly as applied to treponemal diseases where skeletal responses to the various pathogenic subspecies are often shared, challenging the development of a confident diagnosis through osteological observation," co-first author Verena Schuenemann, an archeological sciences, human evolution, and evolutionary medicine researcher affiliated with the University of Tübingen and University of Zurich, said in a statement.

She and her colleagues did whole-genome sequencing on three T. pallidum using isolates, obtained through morphological- and targeted sequencing-based screens on five newborn or infant skeletons going back nearly 350 years from a site in Mexico City. As reported in PLOS Neglected Tropical Diseases today, they found that two of the ancient isolates fell into the syphilis-causing T. pallidum sub-species pallidum, while the remaining isolate coincided with sequences from the T. pallidum sub-species pertenue, known for causing yaws.

In addition to producing the oldest T. pallidum genomes documented so far, the team's findings are expected to inform investigative teams intent on teasing apart treponemal diseases origins. In the past, some researchers argued in favor of New World origins for syphilis, while others speculated that the condition originated at several sites before causing a pandemic syphilis outbreak in 15th century Europe.

"[O]ur finding that two T. pallidum subspecies likely caused similar skeletal manifestations in the past, may suggest a more complex evolutionary history of T. pallidum than previously assumed," co-corresponding author Alexander Herbig, an archeogenetics researcher at Max Planck, said in a statement.

Using Illumina HiSeq 2500 paired-end sequencing, the team sequenced ancient T. pallidum libraries that had been enriched using two round of Agilent array-based hybridization capture, generating between 3.25- and 7.72-fold coverage of each isolate relative to an available reference genome.

The researchers' phylogenetic analyses, which included variants and sequences found in the three ancient genomes and sequences from 39 modern T. pallidum isolates, made it possible to distinguish between clusters of yaws- and syphilis-causing isolates, while exploring relationships within and between these T. pallidum sub-species. They also hinted at potential recombination events between strains in the past, based on a few indefinite SNPs profiles present in the historical strains.

When it came to genes coding for suspected virulence factors, meanwhile, they found evidence for all but one of the candidate virulence-related genes in the ancient T. pallidum genomes. Generally speaking, though, the pathogenicity-related features found in the ancient isolates broadly lined up with those described in contemporary T. pallidum representatives. 

"Although our historic genomes cannot directly contribute to discussions about the origin of syphilis due to their post-Columbian age," the authors wrote, "our study demonstrates the potential of successfully obtaining authentic historic T. pallidum genomes when focusing on treponemal cases in young individuals."