Quantitative analysis of mutation and selection pressures on base composition skews in bacterial chromosomes.

backgroundMost bacterial chromosomes exhibit asymmetry of base composition with respect to leading vs. lagging strands (GC and AT skews). These skews reflect mainly those in protein coding sequences, which are driven by asymmetric mutation pressures during replication and transcription (notably asymmetric cytosine deamination) plus subsequent selection for preferred structures, signals, amino acid or codons. The transcription-associated effects but not the replication-associated effects contribute to the overall skews through the uneven distribution of the coding sequences on the leading and lagging strands.

resultsAnalysis of 185 representative bacterial chromosomes showed diverse and characteristic patterns of skews among different clades. The base composition skews in the coding sequences were used to derive quantitatively the effect of replication-driven mutation plus subsequent selection ('replication-associated pressure', RAP), and the effect of transcription-driven mutation plus subsequent selection at translation level ('transcription-associate pressure', TAP). While different clades exhibit distinct patterns of RAP and TAP, RAP is absent or nearly absent in some bacteria, but TAP is present in all. The selection pressure at the translation level is evident in all bacteria based on the analysis of the skews at the three codon positions. Contribution of asymmetric cytosine deamination was found to be weak to TAP in most phyla, and strong to RAP in all the Proteobacteria but weak in most of the Firmicutes. This possibly reflects the differences in their chromosomal replication machineries. A strong negative correlation between TAP and G+C content and between TAP and chromosomal size were also revealed.

conclusionThe study reveals the diverse mutation and selection forces associated with replication and transcription in various groups of bacteria that shape the distinct patterns of base composition skews in the chromosomes during evolution. Some closely relative species with distinct base composition parameters are uncovered in this study, which also provides opportunities for comparative bioinformatic and genetic investigations to uncover the underlying principles for mutation and selection.