To gain insight into the evolution of the three major clades of the phylogenetic tree we also used a "branch model" where a different d N /d S value is allowed on a "foreground" branch (but d N /d S is averaged along positions in the protein) [103, 104] . This was done in PAML by using "Model = 2". We compared this model to the basic model using a log-likelihood χ 2 test with d.o.f. = 1. For each of the three foreground branches, we used a Bonferroni correction equal to the number of orthogroups present at the branch. We ran this separately for three different "foreground" branches on the phylogenetic tree (labeled in Figure 1 ): A) The branch leading to the Mtb complex; B) The branch leading to pathogenic Mycobacteria; and C) The branch leading to soil-dwelling, non-pathogenic Mycobacteria. The loglikelihood model that we use here compares this branch model to the simple model with a single value of d N /d S described above, and tests whether the model allowing d N /d S to differ on the foreground branch fits the data better than the basic model.