Effects of Genic Base Composition on Growth Rate in G plus C-rich Genomes

The source and significance of the wide variation in the genomic base composition of bacteria have been a matter of continued debate. Although the variation was originally attributed to a strictly neutral process, i.e., species-specific differences in mutational patterns, recent genomic comparisons have shown that bacteria with G+C-rich genomes experience a mutational bias toward A+T. This difference between the mutational input to a genome and its overall base composition suggests the action of natural selection. Here, we examine if selection acts on G+C contents in Caulobacter crescentus and Pseudomonas aeruginosa, which both have very G+C-rich genomes, by testing whether the expression of gene variants that differ only in their base compositions at synonymous sites affects cellular growth rates. In C. crescentus, expression of the more A+T-rich gene variants decelerated growth, indicating that selection on genic base composition is, in part, responsible for the high G+C content of this genome. In contrast, no comparable effect was observed in P. aeruginosa, which has similarly high genome G+C contents. Selection for increased genic G+C-contents in C. crescentus acts independently of the species-specific codon usage pattern and represents an additional selective force operating in bacterial genomes.