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. (C) 2005 Elsevier Ltd. All rights reserved.
Rocha, E. P. C., Smith, J. M., Hurst, L. D., Holden, M. T. G., Cooper, J. E., Smith, N. H., & Feil, E. J. (2006). Comparisons of dN/dS are time dependent for closely related bacterial genomes. Journal of Theoretical Biology, 239(2), 226-235. https://doi.org/10.1016/j.jtbi.2005.08.037