Ancient genomes reveal a deep history of Treponema pallidum in the Americas

Abstract Human treponemal infections are caused by a family of closely related Treponema pallidum that give rise to the diseases yaws, bejel, pinta and, most notably, syphilis1. Debates on a common origin for these pathogens and the history of syphilis itself have weighed evidence for the ‘Columbian hypothesis’2, which argues for an American origin, against that for the ‘pre-Columbian hypothesis’3, which argues for the presence of the disease in Eurasia in the Medieval period and possibly earlier. Although molecular data has provided a genetic basis for distinction of the typed subspecies4, deep evolution of the complex has remained unresolved owing to limitations in the conclusions that can be drawn from the sparse palaeogenomic data that are currently available. Here we explore this evolutionary history through analyses of five pre- and peri-contact ancient treponemal genomes from the Americas that represent ancient relatives of the T. pallidum subsp. pallidum (syphilis), T. pallidum subsp. pertenue (yaws) and T. pallidum subsp. endemicum (bejel) lineages. Our data indicate unexplored diversity and an emergence of T. pallidum that post-dates human occupation in the Americas. Together, these results support an American origin for all T. pallidum characterized at the genomic level, both modern and ancient.