Small Insertions and Deletions Drive Genomic Plasticity during Adaptive Evolution of Yersinia pestis

The life cycle of Yersinia pestis has changed a lot to adapt to flea-borne transmission since it evolved from an enteric pathogen, Yersinia pseudotuberculosis. Small insertions and deletions (indels), especially frameshift mutations, can have major effects on phenotypes and contribute to virulence and host adaptation through gene disruption and inactivation. Here, we analyzed 365 Y. pestis genomes and identified 2,092 genome-wide indels on the core genome. As recently reported in Mycobacterium tuberculosis, we also detected "indel pockets" in Y. pestis, with average complexity scores declining around indel positions, which we speculate might also exist in other prokaryotes. Phylogenic analysis showed that indel-based phylogenic tree could basically reflect the phylogenetic relationships of major phylogroups in Y. pestis, except some inconsistency around the Big Bang polytomy. We observed 83 indels arising in the trunk of the phylogeny, which played a role in accumulation of pseudogenes related to key metabolism and putatively pathogenicity. We also discovered 32 homoplasies at the level of phylogroups and 7 frameshift scars (i.e., disrupted reading frame being rescued by a second frameshift). Additionally, our analysis showed evidence of parallel evolution at the level of genes, with sspA, rpoS, rnd, and YPO0624, having enriched mutations in Brazilian isolates, which might be advantageous for Y. pestis to cope with fluctuating environments. The diversified selection signals observed here demonstrates that indels are important contributors to the adaptive evolution of Y. pestis. Meanwhile, we provide potential targets for further exploration, as some genes/pseudogenes with indels we focus on remain uncharacterized. IMPORTANCE Yersinia pestis, the causative agent of plague, is a highly pathogenic clone of Yersinia pseudotuberculosis. Previous genome-wide SNP analysis provided few adaptive signatures during its evolution. Here by investigating 365 public genomes of Y. pestis, we give a comprehensive overview of general features of genome-wide indels on the core genome and their roles in Y. pestis evolution. Detection of "indel pockets," with average complexity scores declining around indel positions, in both Mycobacterium tuberculosis and Y. pestis, gives us a clue that this phenomenon might appear in other bacterial genomes. Importantly, the identification of four different forms of selection signals in indels would improve our understanding on adaptive evolution of Y. pestis, and provide targets for further physiological mechanism researches of this pathogen. As evolutionary research based on genome-wide indels is still rare in bacteria, our study would be a helpful reference in deciphering the role of indels in other species.