Factors affecting codon usage in Yersinia pestis.

The complete genome of Yersinia pestis which was the causative agent of the systemic invasive infectious disease classically referred as plague, had been recently sequenced. In order to have a further insight into the synonymous codon usage evolution, factors shaping synonymous codon usage pattern of Yersinia pestis were analyzed in this paper. The coding sequences larger than or equal to 300 bp were used in codon usage analysis. Though "G"+"C" content in Y. pestis genome was slightly lower (47.64%), the highly expressed genes tended to use "C" or "G" at synonymous sites compared with lowly expressed genes. Conversely, lowly expressed genes tended to prefer "A" or "T" at synonymous positions. Gene expression level was strongly correlated with the first axis of the correspondence analysis (COA) (R=0.63, P<0.0001). By the analyses of the codon usage pattern of highly and lowly expressed genes, it was confirmed that gene expression level was partially responsible for the codon usage bias. GC-skew analysis showed that codon usage suffered replication-transcriptional selection. Codon adaptation index (CAI), frequency of "C"+"G" at the synonymous third position of codon (GC3s) and the effective number of codons (Nc) values showed some differences among different gene length groups. "G"+"C" content of genes was strongly correlated with the first axis of the COA (R=0.72, P<0.0001). It could be concluded that gene expressivity, replication-transcriptional selection, gene length and gene composition constraints were the main affecting factors of codon usage variation in Y. pestis.