Identification of a bacterial regulatory system for ribonucleotide reductases by phylogenetic profiling.

Using comparative genomics approaches, we analyzed the regulation of ribonucleotide reductase genes in bacterial genomes. A highly conserved palindromic signal with consensus acaCwAtATaTwGtg, named NrdR-box, was identified upstream of most operons encoding ribonuleotide reductases from three different classes. By correlating the occurrence of NrdR-boxes with phylogenetic distribution of ortholog families, we identified a transcriptional regulator containing Zn-ribbon and ATP-cone motifs (COG1327) for the predicted ribonucleotide reductase regulon. Further characterization of the regulon and metabolic reconstruction of the regulated pathways demonstrated its functional link to replication. The method of simultaneous phylogenetic profiling of genes and conserved regulatory signals introduced in this study could be used to identify transcriptional factors regulating orphan regulons.