The [PSI ] yeast prion does not wildly affect proteome composition whereas selective pressure exerted on [PSI ] cells can promote aneuploidy.

The yeast Sup35 protein is a subunit of the translation termination factor, and its conversion to the [PSI ] prion state leads to more translational read-through. Although extensive studies have been done on [PSI ], changes at the proteomic level have not been performed exhaustively. We therefore used a SILAC-based quantitative mass spectrometry approach and identified 4187 proteins from both [psi ] and [PSI ] strains. Surprisingly, there was very little difference between the two proteomes under standard growth conditions. We found however that several [PSI ] strains harbored an additional chromosome, such as chromosome I. Albeit, we found no evidence to support that [PSI ] induces chromosomal instability (CIN). Instead we hypothesized that the selective pressure applied during the establishment of [PSI ]-containing strains could lead to a supernumerary chromosome due to the presence of the ade1-14 selective marker for translational read-through. We therefore verified that there was no prevalence of disomy among newly generated [PSI ] strains in absence of strong selection pressure. We also noticed that low amounts of adenine in media could lead to higher levels of mitochondrial DNA in [PSI ] in ade1-14 cells. Our study has important significance for the establishment and manipulation of yeast strains with the Sup35 prion.