Fig. 3.

Identification of a nonsynonymous change within CYS4 that causes drug sensitivity. (a) Fine-scale mapping of the chr7 QTL. Black and pink lines indicate M and Y/S inheritance, respectively. (b) Plasmid-based complementation tests of six genes. Relative resistance to antenolol is shown for the parental strains (M, Y, and S), the hybrid strains (MY, MS, YS), and for complementation with the M, Y, or S allele from six protein-coding genes. Relative resistance is measured by the minimum growth delay divided by the growth delay of each strain. Strains showing significant levels of resistance are indicated in green. (c) Plasmid-based complementation of resistance to atenolol using chimeric CYS4 constructs. CYS4 constructs include: the M (red), Y (blue), and S (purple) allele; chimeric constructs containing either the coding or noncoding region (NC) from M or S; and single-base substitution constructs that result in a single nonsynonymous change to the M allele (red $) or the wild-type allele (blue $), and a no-insert vector control. (d) Conservation of the CYS4 drug-resistance allele between yeast and mammals.