Single colonies isolated from passages 2, 3, and 4.

<p>(A) Read depth from whole genome sequencing normalized to average depth across the whole genome is shown for 5 single colonies selected from passage 2 of the evolution experiment. Colors indicate changes in allele frequencies at heterozygous positions. Blue indicates an increase in the proportion of the “A” reference allele, while pink indicates an increase in the proportion of the “B” reference allele, signifying losses of heterozygosity. (B) OD600 values for liquid culture growth assays are plotted over time for the wild-type progenitor (black), and the four unique genotypes recovered from passage 2. Growth in rich media without drug, with 1 μg/mL or 256 μg/mL FLC are shown. Error bars are standard errors for three replicates. Tables on the right side indicate average MIC50 and SMG values for these genotypes. (C) Read depth plotted as in (A) for five single colonies selected from passage 3 of the evolution experiment. (D) OD values for liquid culture growth assays are plotted over time for the wild-type progenitor (black), and the two unique genotypes recovered from passage 3. Growth in rich media alone or with 1 μg/mL FLC or 256 μg/mL FLC are shown. Error bars are standard errors for three replicates. Tables on the right side indicate average MIC50 and SMG values for individual genotypes. (E) Read depth plotted as in (A) for the 5 single colonies selected from passage 4 of the evolution experiment.</p> <p>(PDF)</p>