We used AlignACE [97] to search the upstream regions of the genes in these clusters for motifs. We used the methods for operon prediction, selecting upstream regions, and applying AlignACE to prokaryotic genomes as described in McGuire et al. [77] . Briefly, because of the presence of operons in prokaryotes, we must choose the upstream region of the operon head rather than the region immediately upstream of the gene of interest. Since it is more important to include the correct region than to erroneously include extra incorrect regions, we use a loose operon definition and include sequences for several different possibilities if there is any ambiguity. We look upstream of our gene of interest and select all intergenic sequences until we encounter either a divergent intergenic region or an intergenic region longer than 300 bp.