S cerevisiae ERG11 CNVs evolve in response to fluconazole

Copy number variants (CNVs) of ERG11 are known to play a major role in aquisition of resistance to the commonly used azole family of antifungal drugs in many pathogenic yeast species. However, the conditions in which these CNVs arise, and what affects their dynamics, have not been studied. We used a fluorescent reporter to track CNVs at the ERG11 locus in Saccharomyces cerevisiae, to study the effect of different concentrations of fluconazole (strength of selection), and of different temperatures, on CNV formation. We found that ERG11 CNVs emerge reproducibly at the lower end of the tested fluconazole concentrations. With increase in temperature, CNV emergence was generally more rapid, and they had a greater tendency towards fixation. Unexpectedly, all the evolved CNVs were revealed to be full-chromosome aneuploidies of chromosome VIII (on which ERG11 gene is present). This tendency towards aneuploidy is independent of the genomic location of ERG11, and instead appears to be a characteristic of adaptation to fluconazole.