To examine the evolution of entire pathways and gene families, we categorized orthogroups according to GO (Gene Ontology) and GO Slim terms [29] , PFAM domains [30] , metabolic pathways, predicted regulons (sets of genes predicted to be regulated by a common regulatory protein), and groups of genes upregulated under certain lipids (Methods). We also looked for orthogroups undergoing positive selection by calculating the ratio of nonsynonymous to synonymous mutations (the d N /d S ratio). Figure 3 shows several examples of pathway or gene family profiles and the predicted evolutionary events associated with the gene family. The sort of graphic presented in Figure 3 is browsable for every pathway, PFAM, and GO term in our Supplementary Information website. Tables 2 and 3 show the PFAM and GO categories most expanded (with the most orthogroup members) in the Mtb clade relative to the non-pathogenic Mycobacteria, and Tables 4 and 5 show those most expanded in the Mycobacteria relative to the non-Mycobacteria.