Inferring patterns of recombination and divergence with ancient and modern treponemal genomes

The treponemal diseases yaws, bejel and syphilis, all caused by subspecies of the bacterium Treponema pallidum, are re-emerging worldwide, yet their origins and spread remain largely unresolved. Albeit still rare, reconstructed ancient genomes of various T. pallidum strains now exist, to complement the analyses on the modern-day diversity of treponemes. Here, we report a new high-coverage (35X) ancient genome of a historical T. pallidum subsp. pallidum strain from the 17th century. This novel addition, combined with a selection of 76 modern and historical strains, enables a new level of in-depth investigation of treponemal evolution across all human-infecting strains, with detailed analyses on recombination, positive selection, and divergence history of T. pallidum subspecies. Altogether 18 recombinant genes with strong evidence for effects of positive selection are identified, potentially responsible for virulence and immune evasion. The profound impact of recombination is in particular demonstrated in the diversification of the yaws- and bejel-causing clades, as excluding these recombinant genes from phylogenetic analysis causes these well-separated subspecies to cluster into a single clade. Both the involvement of ancient genomes in several recombination events, and the molecular clock dating of the subspecies divergence history emphasize the importance of recombination in the early adaptations of all T. pallidum strains. These findings are crucial in resolving the evolutionary history of T. pallidum, and in understanding the functionalities of treponemes beyond what could be achieved with modern genomic data alone. ### Competing Interest Statement The authors have declared no competing interest.