Shigella species are specialised lineages of Escherichia coli that have converged to become human-adapted and cause dysentery by invading human gut epithelial cells. Most studies of Shigella evolution have been restricted to comparisons of single representatives of each species; and population genomic studies of individual Shigella species have focused on genomic variation caused by single nucleotide variants and ignored the contribution of insertion sequences (IS) which are highly prevalent in Shigella genomes. Here, we investigate the distribution and evolutionary dynamics of IS within populations of Shigella dysenteriae Sd1, Shigella sonnei and Shigella flexneri . We find that five IS (IS 1 , IS 2 , IS 4 , IS 600 and IS 911 ) have undergone expansion in all Shigella species, creating substantial strain-to-strain variation within each population and contributing to convergent patterns of functional gene loss within and between species. We find that IS expansion and genome degradation are most advanced in S . dysenteriae and least advanced in S . sonnei ; and using genome-scale models of metabolism we show that Shigella species display convergent loss of core E . coli metabolic capabilities, with S . sonnei and S . flexneri following a similar trajectory of metabolic streamlining to that of S . dysenteriae . This study highlights the importance of IS to the evolution of Shigella and provides a framework for the investigation of IS dynamics and metabolic reduction in other bacterial species. Author summary Originally classified as a genus due to shared disease features, Shigella species actually represent distinct lineages of Escherichia coli that have become human-restricted dysentery pathogens via convergent evolution. A hallmark of this host-adaptation is the accumulation of insertion sequences (IS), which interrupt genes and cause deletions or genome rearrangements. Due to technical limitations in identifying IS insertions from short-read data, our understanding of the contribution of IS to the evolution of Shigella and other host- restricted bacteria has relied on analyses of either single genome representatives, or small numbers of genomes, and there are no large-scale population genomic studies exploring IS dynamics within bacterial species. Here we explore IS variation within and between Shigella species, revealing their historical and ongoing contributions to evolutionary convergence and metabolic streamlining.
【초록키워드】 Evolution, Variation, Genome, metabolism, Population, Features, pathogen, comparison, Lineage, Deletion, evolutionary dynamics, trajectory, single nucleotide variants, epithelial cells, Pathogens, Bacteria, genomes, expansion, Degradation, convergent evolution, distribution, disease, Single nucleotide variant, nucleotide, strain, framework, Escherichia coli, Gut, insertion sequences, Shigella dysenteriae, technical limitations, Shigella sonnei, Shigella flexneri, accumulation, species, sequence, Comparisons, limitation, genus, genomic variation, insertion, hallmark, deletions, bacterial species, dysentery, insertions, Shigella, MOST, Host, FIVE, prevalent, highlight, caused, provide, analysis, contributing to, reduction in, creating, E . coli, functional gene, genomic study, single genome, 【제목키워드】 Evolution, Impact, convergent evolution, sequence, insertion,