Representative examples of pathways containing evolutionary submodules of enzymes. (a) Clustergrams showing the phylogenetic profiles of individual enzymes in three metabolic pathways. For each clustergram, rows indicate individual enzymes and columns indicate individual genomes. A grey box indicates that the enzyme has been detected in that genome, black boxes indicate that it has not. Hierarchical clustering was performed using Cluster3.0  using Spearman rank correlation coefficients and average linkage. Colored boxes indicate manually assigned groups of enzymes with similar phylogenetic profiles. (b) KEGG pathway representations of the three clustered pathways presented in (a). Enzymes are colored by the groups derived from (a). Within each pathway, groups of similar colored enzymes can be located to specific areas of each pathway, suggesting an evolutionarily cohesive module of function. For example, in diterpenoid biosynthesis, the red cluster of enzymes form a spatially distinct section of the pathway connected to the orange cluster of enzymes, while the green cluster of enzymes appears to form the beginnings of the pathway.