Fig. 1: Foreign chromosomes induce proteotoxic stress in diploid hybrid cells.

a Hundreds of genes are differentially expressed in diploid chromosome replacement lines. The replacement lines were cultured in rich medium at 23 °C and their transcriptomes were examined using RNA-seq. A gene was classified as differentially expressed if the fold-change of a replacement line gene to its parental S. cerevisiae strain was greater than 1.5 with an adjusted p-value < 0.05. The genes on the replaced chromosomes were excluded from the analysis. Common-response genes refer to the genes commonly up- or downregulated in at least four replacement lines. A complete gene list can be found in Supplementary Data 1. b The expression profile of diploid replacement lines is positively correlated with those of wild-type cells under stress conditions and aneuploid cells. The median expression levels in eleven diploid replacement lines were compared to the environmental stress response (ESR) dataset³³ and the aneuploid transcriptome⁴². Spearman’s correlation coefficients were calculated and are shown in the figure. Details of correlations for individual lines are presented in Supplementary Data 2. c Images of Hsp104-mCherry aggregates in diploid S. cerevisiae (Sc) and replacement cell lines. Hsp104 was diffusely localized in the cytosol when cells were grown at 23 °C, but formed foci upon shifting the temperature to 37 °C. Scale bar: 5 μm. These results were reproducible in eight independent experiments. d Diploid replacement lines take longer to dissolve all aggregates upon heat treatments. Yeast strains containing an HSP104-mCherry-URA cassette were grown to exponential phase in YPD at 23 °C and then shifted to 37 °C. The percentage of cells containing Hsp104-mCherry foci was determined 180 min after shifting the temperature. The 12 L line was not included in this assay since HSP104 is located on replaced Chromosome 12 and S. bayanus var uvarum was excluded as they are cryotolerant and cannot tolerate heat treatments (n = 8; N ≥ 500 cells per time-point). Data are presented as mean values +/− SEM. ***: p-value < 10⁻³; one-sided Student’s t-test between S. cerevisiae and replacement lines. Source data and detailed statistical information are provided as a Source Data file.