Codon Usage Domains over Bacterial Chromosomes

Abstract

The geography of codon bias distributions over prokaryotic genomes and its impact upon chromosomal organization are analyzed. To this aim, we introduce a clustering method based on information theory, specifically designed to cluster genes according to their codon usage and apply it to the coding sequences of Escherichia coli and Bacillus subtilis. One of the clusters identified in each of the organisms is found to be related to expression levels, as expected, but other groups feature an over-representation of genes belonging to different functional groups, namely horizontally transferred genes, motility, and intermediary metabolism. Furthermore, we show that genes with a similar bias tend to be close to each other on the chromosome and organized in coherent domains, more extended than operons, demonstrating a role of translation in structuring bacterial chromosomes. It is argued that a sizeable contribution to this effect comes from the dynamical compartimentalization induced by the recycling of tRNAs, leading to gene expression rates dependent on their genomic and expression context. Genomic sequencing projects are clearly showing that cellular components are not randomly encoded over bacterial chromosomes. Order arises for a variety of reasons. Bailly-Bechet and colleagues focused here on the role of translation in shaping bacterial chromosomes. Due to degeneracy of the genetic code, each amino acid can be encoded by multiple codons. Gene encoding is not random, though, and, depending on the genes, some codons are preferred to their synonyms. This is the so-called codon bias phenomenon. The authors analyzed the usage of synonymous codons for protein encoding and its geography over bacterial chromosomes. They found that genes sharing similar codon bias tend to be close to each other on the chromosome, in coherent patches more extended than transcriptional units. Their hypothesis is that those correlations in codon bias enable the cell to locally recycle tRNAs employed during translation, reducing stalling of the ribosomes due to rare tRNAs. This also entails a dependence of expression rates of a gene on its chromosomal context. Furthermore, their analysis made clear that genes involved in anabolic pathways, mainly active when the cell is starving, have a similar codon usage, and that they are encoded on the lagging strand of DNA. They hypothesize that this is due to relative translation efficiency of the lagging strand as compared with the leading one, illustrating the role of translation in creating structural evolutionary constraints.