Produces amino acids (Glu) [18] Corynebacterium efficiens YS-314 Produces amino acids (Glu) [19] Corynebacterium diphtheriae NCTC13129 Y Causes diphtheria [20] Corynebacterium jeikeium K411 Y Causes nocosomial infections [21] Streptomyces avermitilis MA-4680 Soil bacteria;antibiotic-producing [22] Streptomyces coelicolor A3(2) Soil bacteria;antibiotic producing [23] Acidothermus cellulolyticus 11B Hot springs of Yellowstone [24] Rhodobacter sphaeroides Gram -, motile; photosyn.; fixes N 2 [14] in yogurt). We extend this comparative analysis to other more distantly related Actinobacteria to yield additional insight into evolutionary trends. We examined protein evolution across these 31 organisms, both at the nucleotide level and at the level of protein families, including studying gene families associated with the transition from nonpathogenic soil-dwelling bacteria to obligate pathogens. Our results highlight the importance of lipid metabolism and its regulation, and reveal differences in the evolutionary profiles for genes implicated in saturated and unsaturated fatty acid metabolism. Our analysis also suggests that DNA repair and molybdopterin cofactors are expanded in pathogenic Mycobacteria and Mtb.