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Yersinia pestis , the causative agent of plague, is best known for historical pandemics, but still actively causes disease in many parts of the world.  Y. pestis  is a recently derived clone of the pathogenic species  Yersinia pseudotuberculosis , but is more associated with human infection. Numerous studies have documented genomic changes since the two species differentiated, although all of these studies used a relatively small sample set for defining these differences. In this study, we compared the complete genomic content between a diverse set of  Y. pestis  and  Y. pseudotuberculosis  genomes, and identified unique loci that could serve as diagnostic markers or for better understanding the evolution and pathogenesis of each group. Comparative genomics analyses also identified subtle variations in gene content between individual monophyletic clades within these species, based on a core genome single nucleotide polymorphism phylogeny that would have been undetected in a less comprehensive genome dataset. We also screened loci that were identified in other published studies as unique to either species and generally found a non-uniform distribution, suggesting that the assignment of these unique genes to either species should be re-evaluated in the context of current sequencing efforts. Overall, this study provides a high-resolution view into the genomic differences between  Y. pestis  and  Y. pseudotuberculosis , demonstrating fine-scale differentiation and unique gene composition in both species.

Redefining the differences in gene content between Yersinia pestis and Yersinia pseudotuberculosis using large-scale comparative genomics