[SP14+] prions display non-Mendelian inheritance and mitotic instability. (A) A representative tetrad from a cross of [SP14+] to [sp14−] illustrated epigenetic inheritance of the prion phenotype. (B) [SP14+], weak (w) [PSI+], [psi−], an SP14/SUP35 [PRION+] diploid (containing one copy of SP14 and one copy of SUP35), and a tetrad from the SP14/SUP35 [PRION+] diploid were spotted onto YPD and SD-ade media. The relative strength of nonsense suppression in the progeny is described as strong (s), medium (m), or weak (w). The SUP35 allele expressed in the progeny is indicated parenthetically. (C) The original isolate of [SP14+] and phenotypically weak and strong [SP14+] variants were plated on YPD and analyzed for prion loss (red colonies). Prion loss was calculated as the change compared to the most stable [SP14+] variant.