Dynamics of Genome Rearrangement in Bacterial Populations

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Abstract
Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of “symmetric inversions”—inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings represent the first characterization of genome arrangement evolution in a bacterial population evolving outside laboratory conditions. Insight into the process of genomic rearrangement may further the understanding of pathogen population dynamics and selection on the architecture of circular bacterial chromosomes. Whole-genome sequencing has revealed that organisms exhibit extreme variability in chromosome structure. One common type of chromosome structure variation is genome arrangement variation: changes in the ordering of genes on the chromosome. Not only do we find differences in genome arrangement across species, but in some organisms, members of the same species have radically different genome arrangements. We studied the evolution of genome arrangement in pathogenic bacteria from the genus Yersinia. The Yersinia exhibit substantial variation in genome arrangement both within and across species. We reconstructed the history of genome rearrangement by inversion in a group of eight Yersinia, and we statistically quantified the forces shaping their genome arrangement evolution. In particular, we discovered an excess of rearrangement activity near the origin of chromosomal replication and found evidence for a preferred configuration for the relative orientations of the origin and terminus of replication. We also found real inversions to be significantly shorter than expected. Finally, we discovered that no single reconstruction of inversion history is parsimonious with respect to the total number of inversion mutations, but on average, reconstructed genome arrangements favor “balanced” genomes—where the replication origin is positioned opposite the terminus on the circular chromosome.