[PSI+] Prion transmission barriers protect Saccharomyces cerevisiae from infection: intraspecies 'species barriers'

Abstract

[PSI+] is a prion of Sup35p, an essential translation termination and mRNA turnover factor. The existence of lethal [PSI+] variants, the absence of [PSI+] in wild strains, the mRNA turnover function of the Sup35p prion domain, and the stress reaction to prion infection suggest that [PSI+] is a disease. Nonetheless, others have proposed that [PSI+] and other yeast prions benefit their hosts. We find that wild Saccharomyces cerevisiae strains are polymorphic for the sequence of the prion domain and particularly in the adjacent M domain. Here we establish that these variations within the species produce barriers to prion transmission. The barriers are partially asymmetric in some cases, and evidence for variant specificity in barriers is presented. We propose that, as the PrP 129M/V polymorphism protects people from Creutzfeldt-Jakob disease, the Sup35p polymorphisms were selected to protect yeast cells from prion infection. In one prion incompatibility group, the barrier is due to N109S in the Sup35 prion domain and several changes in the middle (M) domain, with either the single N109S mutation or the group of M changes (without the N109S) producing a barrier. In another, the barrier is due to a large deletion in the repeat domain. All are outside the region previously believed to determine transmission compatibility. [SWI+], a prion of the chromatin remodeling factor Swi1p, was also proposed to benefit its host. We find that none of 70 wild strains carry this prion, suggesting that it is not beneficial.

Figure 1

Distribution of mutations in Sup35p of wild strains of S. cerevisiae. The width of the vertical lines marking the location of mutations is in rough proportion to their frequency (Table S3). The box on the left is a region in which mutation can block [PSI+] transmission (Depace et al. 1998). Boldface, underlined text indicates those mutations observed most frequently. The location of the octapeptide repeats is shown as >>>>>.

Figure 2

Interaction of Sup35p polymorphs with each other. In [PSI+], strains of one polymorph is expressed Sup35NM–GFP of another (or the same) polymorph, and the appearance of the GFP fluorescence as dots indicates association of the indicated NM–GFP with the Sup35 prion aggregates. Strain 4828 with each prion (rows) was transformed with plasmids expressing the polymorph NM–GFP (columns) fusion proteins from the ADH1 promoter and cells were examined as described in methods. GFP expressed alone (and not fused to Sup35) is evenly distributed in the cytoplasm. A8NM–GFP does differ by one residue (P186A) from the G2 sequence.