The effect of spontaneous mutations on CUP1 copy number and copper tolerance in Saccharomyces cerevisiae

Genomic regions containing tandem duplications may be subject to particularly high rates of copy number mutations due to recombinational repair of DNA damage. Consequently, changes in copy number may be among the most accessible beneficial mutations during evolution in a new environment. In the budding yeast Saccharomyces cerevisiae, the gene CUP1 occurs in multiple tandem copies and encodes a metallothionein relevant for copper homeostasis. We examined CUP1 copy number in 220 mutation accumulation lines and their ancestors to quantify spontaneous genetic change at this locus. We also measured copper tolerance in these strains to understand the phenotypic effects of CUP1 copy number change and other mutations. Mutations in CUP1 copy number occurred relatively rapidly, with a bias towards losses. While copper tolerance also declined due to mutations, this change was less rapid and was only partly driven by CUP1 copy number. Thus, while CUP1 is highly susceptible to copy number change, our results add to a body of evidence that these accessible mutations on their own do not fully account for variation in copper tolerance.