Fig. 2: Proteotoxic stress-induced incompatibility leads to mitotic and meiotic defects.

a Growth rates of diploid replacement lines are significantly reduced when Hsp90 is mildly compromised. The doubling time of S. cerevisiae (Sc), S. bayanus var uvarum (Sb), and replacement lines was measured and compared with or without the Hsp90 inhibitor, Geldanamycin (50 μM GdA), at 23 °C (n = 3). b The growth defect is not specific to compromised Hsp90. When replacement lines were grown in YPD at 32 °C, the doubling time is highly correlated with the data for cells treated with GdA (n = 3, Spearmans ρ = 0.83, p = 0.03). c Several replacement lines exhibit significant meiotic defects when pre-treated with a low dosage of GdA. Cells were grown in pre-sporulation medium with 50 μM GdA and then induced to sporulate under normal conditions without GdA (n = 4). The temperature was always maintained at 23 °C. Sensitivity was calculated as 1 - (sporulation frequency with GdA pre-treatment/sporulation frequency without GdA pre-treatment) and compared to both parents. d, Growth defects of the 16L and 8+15L lines can be partially rescued by providing a complete set of Sc or Sb genomes. The 16L and 8+15L haploid cells were mated with S. cerevisiae (16L × Sc and 8+15L × Sc) or S. bayanus var uvarum (16L × Sb and 8+15L × Sb) to generate heterozygous diploid cells and their doubling time was measured in the presence of 50 μM GdA. The doubling time of homozygous diploid replacement lines was compared to that of the heterozygous diploids (n = 3). e The fitness defect under GdA treatment (50 μM) is significantly correlated with the number of complexes having subunits encoded on the replaced chromosomes (Spearmans ρ = 0.68, p = 0.025). f The percentages of cells containing Hsp104-mCherry foci are significantly correlated with the number of complexes having subunits encoded on the replaced chromosomes (Spearmans ρ = 0.68, p = 0.03). Hsp104 aggregates were counted in cells after having been shifted to 37 °C for 180 min (n = 8, N ≥ 500 cells per time-point). The data are presented as mean values +/− SEM. ***: p-value < 10⁻³, one-sided Student’s t-test. Source data and detailed statistical information are provided as a Source Data file.