Gene duplication and divergence drive genomic diversity of Orientia tsutsugamushi

Orientia tsutsugamushi, formerly Rickettsia tsutsugamushi, is an obligate intracellular bacterium that causes scrub typhus, an acute febrile disease with high morbidity and diverse clinical presentation. Scrub typhus is transmitted by Leptotrombidium chigger mites and characterized by a largely irregular geographic distribution. The disease is endemic to regions of Southeast Asia, Australia, and the Middle East, encompassing over 1 billion people, but the distribution is expanding with recent cases reported from Europe and Africa. Previous work to understand population genetics in O. tsutsugamushi has been based on subgenomic sampling methods, and whole genome characterization has been based on analyses of single genomes. In this study, we compared 40 whole genomes from geographically dispersed areas and confirm patterns of extensive homologous recombination likely driven by repetitive sequences. High rates of recombination among O. tsutsugamushi genomes appear to have eliminated any clonal frame, but have not completely degraded phylogenetic signals, allowing us to infer evolutionary relationships. Unlike other highly recombinant species where the uptake of exogenous DNA drives genomic diversity, the pan-genome of O. tsutsugamushi is driven by mechanisms of duplication and subsequent divergence. The unusual evolutionary characteristics of O. tsutsugamushi expand our present understanding of bacterial evolutionary mechanisms while highlighting limitations of existing comparative genomics tools when dealing with highly recombinant species.