In addition to gene family expansions, we observe evidence for selection on the coding sequence of lipid metabolism genes. In our d N /d S calculations, we observe enrichment for positive selection in lipid degradation genes on the branch leading to the pathogenic Mycobacteria (Additional file 1: Table S2 ). For example, Rv2524c, the multifunctional FAS-I polypeptide utilized during de novo fatty synthesis [35] , has the second highest d N /d S value on this branch. Additional lipid metabolism genes with elevated d N /d S values include 15 genes predicted to be involved in the β-oxidation pathway of fatty acid degradation: seven fadE (acyl coA dehydrogenase) genes, three fadD (fatty acid CoA ligase) genes, two fadB (NADPH quinone oxidoreductase/3-hydroxybutyryl-CoA dehydrogenase) genes, one fadA (acetyl-CoA acyltransferase) gene, and two echA (enoyl-CoA hydratase) genes. Hence, we observe expansions of lipid biosynthesis genes, as well as observing evidence for positive selection acting on genes within the β-oxidation pathway. Both the lipid biosynthesis and lipid degradation pathways are specialized within the pathogenic Mycobacteria. This expansion could possibly benefit the pathogen in a manner to accommodate production and modification of cell wall lipids involved in manipulation of host immune response. The lipid degradation is particularly beneficial for the long term survival of the pathogen metabolizing host lipids encountered during infection.