title: Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites.
abstract: The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites.
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tamarit
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Siv G E
authors.initials: SGE
authors.lastname: Andersson
mesh_terms: D000596:Amino Acids / Q000235:genetics; D001482:Base Composition; D003062:Codon; D006194:Gardnerella vaginalis / Q000235:genetics*; D048668:Lactobacillus delbrueckii / Q000235:genetics*; D052197:Limosilactobacillus fermentum / Q000235:genetics*; D010802:Phylogeny
chemical_list: D000596:Amino Acids; D003062:Codon
keywords: Bifidobacterium; Lactobacillus; codon usage; mutation bias; optimal codon