Genomic Arrangement of Regulons in Bacterial Genomes

Regulons, as groups of transcriptionally co-regulated operons, are the basic units of cellular response systems in bacterial cells. While the concept has been long and widely used in bacterial studies since it was first proposed in 1964, very little is known about how its component operons are arranged in a bacterial genome. We present a computational study to elucidate of the organizational principles of regulons in a bacterial genome, based on the experimentally validated regulons of E. coli and B. subtilis. Our results indicate that (1) genomic locations of transcriptional factors (TFs) are under stronger evolutionary constraints than those of the operons they regulate so changing a TF's genomic location will have larger impact to the bacterium than changing the genomic position of any of its target operons; (2) operons of regulons are generally not uniformly distributed in the genome but tend to form a few closely located clusters, which generally consist of genes working in the same metabolic pathways; and (3) the global arrangement of the component operons of all the regulons in a genome tends to minimize a simple scoring function, indicating that the global arrangement of regulons follows simple organizational principles.