Figure 4. Small differences in target size and differences in basal mutation rate are responsible for the observed differences drug resistance rate.
(a) The target size (the number of mutations conferring rifampicin resistance) of each strain under each condition was determined by sequencing the rifampicin resistance determining region of 100 isolates from each strain in each condition. Each mutation is shown on the x-axis, with coordinates representing position within rpoB (Rv0667). The number of mutants per strain uniquely formed within a culture is shown on the y-axis. The Lineage 4 strain, CDC1551, is shown in red; the Lineage 2 strain is shown in blue. On the right, the target size - the number of unique mutations conferring rifampicin resistance – is shown. (b) The per base pair mutation rate is determined by normalizing the drug resistance rate by target size. Drug concentration is shown on the x-axis, mutation rate per base pair is shown on a linear scale on the y-axis. Lineage 4 is shown in red; Lineage 2 is shown in blue. Significance was determined by comparing strain pairs using the Wilcoxon rank-sum test; error bars represent 95% confidence intervals. Values are found in Supplementary Table 4.