Inference and Analysis of the Relative Stability of Bacterial Chromosomes

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Abstract
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 computes 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 intrinsic measure of genome stability that allowed the comparison of distantly related genomes and the inference of ancestral states. This shows that clades differ in genome stability, with cyanobacteria being the least stable and γ-proteobacteria the most stable. Without correction for phylogeny, free-living bacteria are the least stable group of genomes, followed by pathogens, and then endomutualists. However, after correction for phylogenetic inertia (or the removal of cyanobacteria from the analysis), there is no significant association between genome stability and lifestyle or genome size. Hence, although this method has allowed uncovering some of mechanisms leading to rearrangements, we still ignore the forces that differentially shape selection upon genome stability in different species.