Insights into the evolution of <i>Yersinia pestis</i> through whole-genome comparison with <i>Yersinia pseudotuberculosis</i>

<jats:p> <jats:italic>Yersinia pestis</jats:italic> , the causative agent of plague, is a highly uniform clone that diverged recently from the enteric pathogen <jats:italic>Yersinia pseudotuberculosis</jats:italic> . Despite their close genetic relationship, they differ radically in their pathogenicity and transmission. Here, we report the complete genomic sequence of <jats:italic>Y. pseudotuberculosis</jats:italic> IP32953 and its use for detailed genome comparisons with available <jats:italic>Y. pestis</jats:italic> sequences. Analyses of identified differences across a panel of <jats:italic>Yersinia</jats:italic> isolates from around the world reveal 32 <jats:italic>Y. pestis</jats:italic> chromosomal genes that, together with the two <jats:italic>Y. pestis</jats:italic> -specific plasmids, to our knowledge, represent the only new genetic material in <jats:italic>Y. pestis</jats:italic> acquired since the the divergence from <jats:italic>Y. pseudotuberculosis</jats:italic> . In contrast, 149 other pseudogenes (doubling the previous estimate) and 317 genes absent from <jats:italic>Y. pestis</jats:italic> were detected, indicating that as many as 13% of <jats:italic>Y. pseudotuberculosis</jats:italic> genes no longer function in <jats:italic>Y. pestis</jats:italic> . Extensive insertion sequence-mediated genome rearrangements and reductive evolution through massive gene loss, resulting in elimination and modification of preexisting gene expression pathways, appear to be more important than acquisition of genes in the evolution of <jats:italic>Y. pestis</jats:italic> . These results provide a sobering example of how a highly virulent epidemic clone can suddenly emerge from a less virulent, closely related progenitor. </jats:p>