Prediction of Co-Regulated Genes in Bacillus subtilis Based on the Conserved Upstream Elements across Three Closely Related Species

Abstract

Transcriptional regulatory networks in an organism play an important role for controlling many biological phenomena, such as development and proliferation. Even in bacteria, elucidation of such networks or identification of co-regulated genes is essential in understanding many cellular processes. Moreover, it provides hints toward identifying gene function because co-regulated genes are likely to function for the same purpose. To identify co-regulated genes, the microarray technique, which enables us to monitor the expression levels of thousands of genes in parallel, appears very powerful. However, even if we can ignore its experimental artifacts, it is not always easy to set experimental conditions to identify differential expression patterns of uncharacterized genes. Thus, it would be desirable to develop some computational methods that can supplement such experimental techniques. Although co-regulated genes should have at least one common sequence element, it is generally difficult to identify these genes from the presence of this element because it is very easily obscured by noises. To overcome this problem, we used the conservation information of three closely related species: Bacillus subtilis, Bacillus halodurans, and Bacillus stearothermophilus. Our method consists of two parts; first, we identified Phylogenetically Conserved Elements (PCEs) in the upstream intergenic regions of B.subtilis genes; then, they were clustered according to the similarity of PCEs in their upstream region. We could identify many known and plausible co-regulated genes with this approach.