The yeast Saccharomyces cerevisiae is known as an organism with stable genome and low dependency on respiration. S. cerevisiae ferments glucose as a major source of energy; unlike other fungi in the presence of glucose S. cerevisiae can survive without respiration. In the lab most of the mutations that were identified as conferring resistance and sensitivity to drugs were recessive point mutations or deletions of genes. Yet, in nature other types of mutations, especially copy number variations, are frequent. We wanted to select mutants that confer resistance to drugs and are not through homozygote recessive mutations. To this end we exposed tetraploid yeast to canavanine a toxic analog of arginine. While in haploid yeast canavanine resistance is through a recessive mutation in arginine permease, in tetraploid yeast the resistant colonies had severe genome instability with multiple aneuploidy. In addition, these canavanine resistant colonies totally depend on respiration for drug resistance. In the meeting we will show how mitochondrial functions and genome instability confer resistance to canavanine.