The role of aneuploidies in drug resistance
(A) We calculated the median relative coverage per gene for all samples analyzed in this work. This parameter appeared to be correlated with the distance to the telomere (STAR Methods), so that the log2 ratio to the YPD (of the corresponding strain) was used as a proxy for the gene copy number. Shown is the rolling-median of this value for windows of 50 genes and chromosomes where large duplications were observed (chromosomes E, I, A, and L). Data for chromosomes I, A and L are shown only for those strains in which aneuploidies are observed. Each column corresponds to a sample (ordered as in Figure 6), and the “∗” and “X” correspond to FinA samples in which the parent (FLZ) aneuploidy was maintained or lost, respectively. ERG11, PDR1, and TPO3 are genes that we speculate could be driving the selective advantage of the aneuploidy (see Results). All of the values were cut off at 1.0 (2× coverage as compared to the YPD) for clarity.
(B) Survival of Galleria mellonella larvae during 6 days after inoculation of EB0911 (WT strain) and 2 flz resistant progenies: 3B_FLZ (without aneuploidies) and 3H_FLZ (presenting both ChrE and ChrI duplications).