Tools for opening new chapters in the book of Treponema pallidum evolutionary history

Treponema pallidum infections causing yaws disease and venereal syphilis are globally widespread in human populations, infecting hundreds of thousands and millions annually respectively; endemic syphilis is much less common, and pinta has not been observed in decades. We discuss controversy surrounding the origin, evolution and history of these pathogens in light of available molecular and anthropological evidence. These bacteria (or close relatives) seem to affect many wild African nonhuman primate (NHP) species, though to date only a single NHP Treponema pallidum genome has been published, hindering detection of spillover events and our understanding of potential wildlife reservoirs. Similarly, only ten genomes of Treponema pallidum infecting humans have been published, impeding a full understanding of their diversity and evolutionary history. Research efforts have been hampered by the difficulty of culturing and propagating Treponema pallidum. Here we highlight avenues of research recently opened by the coupling of hybridization capture and next-generation sequencing. We present data generated with such an approach suggesting that asymptomatic bones from NHP occasionally contain enough treponemal DNA to recover large fractions of their genomes. We expect that these methods, which naturally can be applied to modern biopsy samples and ancient human bones, will soon considerably improve our understanding of these enigmatic pathogens and lay rest to old yet unresolved controversies.