title: Comparisons of dN/dS are time dependent for closely related bacterial genomes.
abstract: The ratio of non-synonymous (dN) to synonymous (dS) changes between taxa is frequently computed to assay the strength and direction of selection. Here we note that for comparisons between closely related strains and/or species a second parameter needs to be considered, namely the time since divergence of the two sequences under scrutiny. We demonstrate that a simple time lag model provides a general, parsimonious explanation of the extensive variation in the dN/dS ratio seen when comparing closely related bacterial genomes. We explore this model through simulation and comparative genomics, and suggest a role for hitch-hiking in the accumulation of non-synonymous mutations. We also note taxon-specific differences in the change of dN/dS over time, which may indicate variation in selection, or in population genetics parameters such as population size or the rate of recombination. The effect of comparing intra-species polymorphism and inter-species substitution, and the problems associated with these concepts for asexual prokaryotes, are also discussed. We conclude that, because of the critical effect of time since divergence, inter-taxa comparisons are only possible by comparing trajectories of dN/dS over time and it is not valid to compare taxa on the basis of single time points.
authors.affiliation: Atelier de BioInformatique, Université Paris VI, 75005 Paris, France.
authors.forename: Eduardo P C
authors.initials: EP
authors.lastname: Rocha
authors.forename: John Maynard
authors.initials: JM
authors.lastname: Smith
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Cooper
authors.forename: Noel H
authors.initials: NH
authors.lastname: Smith
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
mesh_terms: D001419:Bacteria / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D016680:Genome, Bacterial; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic; D013269:Stochastic Processes