Inference and analysis of the relative stability of bacterial chromosomes

The stability of genomes is highly variable, both in terms of gene content and gene order. Here I calibrate the loss of gene order conservation (GOC) through time by fitting a simple probabilistic model on pairwise comparisons involving 126 bacterial genomes. The model cornputes the probability of separation of pairs of contiguous genes per unit of time and fits the data better than previous ones while allowing a mechanistic interpretation for the loss of GOC with time. Although the information on operons is not used in the model, I observe, as expected, that most highly conserved pairs of genes are indeed within operons. However, even the other pairs are much more conserved than expected given the observed experimental rearrangement rates. After 500 Myr about 50% of the originally contiguous orthologues remain so in the average genome. Hence. the large majority of rearrangements Must be deleterious and random genome rearrangements are unlikely to provide for positively selected structural changes. I then use the deviations from the model to define an o intrinsic measure of genorne stability that allowed the comparison of distantly related gerionles and file inference of ancestral states. This shows that clades differ in genonie stability, with cyanobacteria being the least stable and gamma-proteobacteria the most stable. Without correction for phylogeny, free-living bacteria tire the least stable group of genomes, followed by pathogens, and then endormutualalists. However, after correction for phylogenetic inertia (or the removal of cyanobacteria frorn the analysis), there is no significant associafion between genome stability and lifestyle or genome size. Hence, although this method has allowed uncovering sonic of mechanisms leadin to rearrangements, we still ignore the forces that differentially shape selection upon genome stability in different species.