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Author summary Among the worldwide prevalent treponemal diseases syphilis is a global threat that is currently re-emerging. The origins of syphilis and other treponemal diseases are as yet unresolved and are subject to an intensive scholarly debate. Until now, assumptions on its origins and evolutionary history could only be drawn from osteological analyses of past cases and genetic analysis of contemporary T. pallidum genomes; contributions from ancient DNA are very rare and have so far failed to provide genome-level data. The ancient T. pallidum genomes presented here allow us, for the first time, to perform genome-wide comparative analyses and to assess a connection between osteological manifestations of past treponemal cases and specific T. pallidum species. Our study demonstrates the possibility of retrieving ancient T. pallidum genomes from archeological material and thereby establishes a new method that could greatly contribute to uncover the mystery regarding the origins of treponemal diseases.
