Replication-associated inversions are the dominant form of bacterial chromosome structural variation

Abstract

Structural arrangement of a bacterial chromosome varies widely between closely related species and can result in significant phenotypic outcomes. The appearance of large-scale chromosomal inversions that are symmetric relative to the dnaA gene (usually linked to oriC, the origin of replication) has been previously observed; however, the overall prevalence of replication-associated structural rearrangements (RASRs) in bacteria and their causal mechanisms are currently unknown. The decreased cost of full-length genome sequencing has led to a rapidly growing collection of complete genomes spanning multiple different clades, therefore allowing an opportunity to examine chromosomal inversions in the context of species spanning diverse phylogenetic classifications. Here we systematically identify the locations of large, chromosomal inversions in species with multiple complete sequenced genomes using the Refseq and Genbank NCBI databases to investigate potential mediating biological mechanisms. Out of the 239 species available with 10 or more complete genomes, 206 contained sequences with at least one large ([≥]50Kb) inversion in their set of within-species sequence comparisons. We observed 73.4% of the 127,161 large inversions were centered at a point within 10% proportionate distance to the annotated dnaA gene, which is often nearby the origin of replication. Inversions offset from the annotated dnaA sequence were generally confirmed to be centered on the actual origin of replication. Equidistant breakpoints from the replication origin and prevalence of flanking repeats provide evidence that the breaks that are formed during the replication process are then repaired to opposing positions. We also found a strong relationship between the later stages of replication and the range in variation of distance from symmetry, suggesting that replication fork arrest may be a mechanistic cause for the asymmetry in some inversions.