Fig. 7.

Lineage-specific adaptive variation in M. tuberculosis genes enriched in necrotic granulomas.

(A and B) Distribution plots comparing the frequency of lineage-specific nonsynonymous (A) or synonymous (B) mutations in the M. tuberculosis homologs of the top 50 granuloma-specific genes (red bars) to a simulated distribution of random mutations in this gene set (gray bars). n = 1000 simulation events; a one-sided (right-tailed) permutation test was used to determine P values. (C) Phylogenetic trees of 69 M. tuberculosis clinical isolates representing the seven primary lineages (L1 to L7) and several major sublineages, including L4.1 to L4.9 with mutational events for representative granuloma-specific genes (i) mmpL9 and (ii) Rv1215c highlighted. Blue squares represent nonsynonymous mutations, and the green circle represents a synonymous mutation. Branch colors indicate the inferred lineages.