title: Function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size.
abstract: Changes in effective population size impinge on patterns of molecular evolution. Notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. This prediction has been validated empirically for several endosymbiont and island taxa. Here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidates for reduced effective population size: Bacillus anthracis, Bordetella parapertussis, Mycobacterium leprae, Salmonella enterica typhi, Shigella spp., and Yersinia pestis. Using closely related genomes to analyze substitution rate dynamics across six phylogenetically independent bacterial clades, we demonstrate that relative rates of coding sequence evolution are biased according to gene functional category. Notably, genes that buffer against slightly deleterious mutations, such as chaperones, experience stronger rate accelerations than other functional classes at both nonsynonymous and synonymous sites. Although theory predicts altered evolutionary dynamics for buffer loci in the face of accumulating deleterious mutations, to observe even stronger rate accelerations is surprising. We suggest that buffer loci experience elevated substitution rates because the accumulation of deleterious mutations in the remainder of the genome favors compensatory substitutions in trans. Critically, the hyper-acceleration is evident across phylogenetically independent clades, supporting the hypothesis that reductions in effective population size predictably induce epistatic responses in genes that buffer against slightly deleterious mutations.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK. Tobias.Warnecke@crg.es
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.forename: Eduardo P C
authors.initials: EP
authors.lastname: Rocha
mesh_terms: D000465:Algorithms; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D001482:Base Composition / Q000235:genetics; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D011156:Population Density