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

EPC Rocha, JM Smith, LD Hurst, MTG Holden, JE Cooper, NH Smith, EJ Feil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

309 Citations (Scopus)

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. (C) 2005 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)226-235
Number of pages10
JournalJournal of Theoretical Biology
Volume239
Issue number2
DOIs
Publication statusPublished - 21 Mar 2006

Keywords

  • bacterial evolution
  • dN/dS ratio
  • purifying selection
  • SEQUENCE TYPING SYSTEM
  • AMINO-ACID SITES
  • MYCOBACTERIUM-TUBERCULOSIS
  • NUCLEOTIDE POLYMORPHISMS
  • STAPHYLOCOCCUS-AUREUS
  • BACILLUS-ANTHRACIS
  • GENE
  • SELECTION
  • POPULATION
  • EVOLUTION

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