Figure 4

Intra-patient evolution and mutation rates. (A) Phylogenetic placement of patient isolates relative to the most closely related isolates from a global M. tuberculosis collection (46). A thyA P17L mutation possibly conferring para-aminosalicylic acid (PAS) resistance was acquired some time on the branch leading to the patient isolates. sSNP, synonymous SNP. (B) Detailed phylogeny of patient isolates with resistance-conferring mutations mapped on the branches. (C) Example of hitchhiking SNPs. Frequency of SNPs conferring resistance to FLQ (gyrB) and ETH (mshA) in sequencing reads over time (months) as well as hitchhiking SNPs (grey shading) with correlation coefficients >0.9 relative to any gyrB or mshA resistance SNP. (D) Box plot of calculated pairwise mutation rates per year between any pair of isolates using three different SNP exclusion criteria: Set I, all SNPs included; Set II, resistance mutations excluded; Set III, resistance mutations and hitchhiking SNPs excluded.