Resistance to Arsenite and Arsenate in Saccharomyces cerevisiae Arises through the Subtelomeric Expansion of a Cluster of Yeast Genes

Arsenic is one of the most prevalent toxic elements in the environment, and its toxicityaffects every organism. Arsenic resistance has mainly been observed in microorganisms, and, inbacteria, it has been associated with the presence of the Ars operon. In Saccharomyces cerevisiae, threegenes confer arsenic resistance: ARR1, ARR2, and ARR3. Unlike bacteria, in which the presence ofthe Ars genes confers per se resistance to arsenic, most of the S. cerevisiae isolates present the threeARR genes, regardless of whether the strain is resistant or sensitive to arsenic. To assess the geneticfeatures that make natural S. cerevisiae strains resistant to arsenic, we used a combination ofcomparative genomic hybridization, whole-genome sequencing, and transcriptomics profiling withmicroarray analyses. We observed that both the presence and the genomic location of multiplecopies of the whole cluster of ARR genes were central to the escape from subtelomeric silencing andthe acquisition of resistance to arsenic. As a result of the repositioning, the ARR genes wereexpressed even in the absence of arsenic. In addition to their relevance in improving ourunderstanding of the mechanism of arsenic resistance in yeast, these results provide evidence for anew cluster of functionally related genes that are independently duplicated and translocated.