Comparisons of dN/dS are time dependent for closely related bacterial genomes

J Theor Biol. 2006 Mar 21;239(2):226-35. doi: 10.1016/j.jtbi.2005.08.037. Epub 2005 Oct 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / classification
  • Bacteria / genetics*
  • Evolution, Molecular
  • Genetic Variation
  • Genome, Bacterial*
  • Models, Genetic*
  • Mutation
  • Selection, Genetic
  • Stochastic Processes