Codon Usages of Genes on Chromosome, and Surprisingly, Genes in Plasmid are Primarily Affected by Strand-specific Mutational Biases in Lawsonia intracellularis

In this study, the factors driving genome-wide patterns of codon usages in Lawsonia intracellularis genome are determined. For genes on the chromosome of the bacterium, it is found that the most important source of variation results from strand-specific mutational biases. A lesser trend of variation is attributable to genes that are presumed as horizontally transferred. These putative alien genes are unusually GC richer than the other genes, whereas horizontally transferred genes have been observed to be AT rich in bacteria with medium and relatively low G + C contents. Hydropathy of encoded protein and expression level are also found to influence codon usage. Therefore, codon usage in L. intracellularis chromosome is the result of a complex balance among the different mutational and selectional factors. When analyzing genes in the largest plasmid, for the first time it is found that the strand-specific mutational biases are responsible for the primary variation of codon usages in plasmid. Genes, particularly highly expressed genes of this plasmid, are mainly located on the leading strands and this supposed to be the effects exerted by replicational–transcriptional selection. These facts suggest that this plasmid adopts the similar mechanism of replication as the chromosome in L. intracellularis. Common characters among the 10 bacteria in whose genomes the strand-specific mutational biases are the primary source of variation of codon usage are also investigated. For example, it is found that genes dnaT and fis that are involved in DNA replication initiation and re-initiation pathways are absent in all of the 10 bacteria.