Sex, prions, and plasmids in yeast

Abstract

Even deadly prions may be widespread in nature if they spread by infection faster than they kill off their hosts. The yeast prions [PSI+] and [URE3] (amyloids of Sup35p and Ure2p) were not found in 70 wild strains, while [PIN+] (amyloid of Rnq1p) was found in ∼16% of the same population. Yeast prion infection occurs only by mating, balancing the detrimental effects of carrying the prion. We estimated the frequency of outcross mating as about 1% of mitotic doublings from the known detriment of carrying the 2-μm DNA plasmid (∼1%) and its frequency in wild populations (38/70). We also estimated the fraction of total matings that are outcross matings (∼23-46%) from the fraction of heterozygosity at the highly polymorphic RNQ1 locus (∼46%). These results show that the detriment of carrying even the mildest forms of [PSI+], [URE3], or [PIN+] is greater than 1%. We find that Rnq1p polymorphisms in wild strains include several premature stop codon alleles that cannot propagate [PIN+] from the reference allele and others with several small deletions and point mutations which show a small transmission barrier. Wild strains carrying [PIN+] are far more likely to be heterozygous at RNQ1 and other loci than are [pin-] strains, probably reflecting its being a sexually transmitted disease. Because sequence differences are known to block prion propagation or ameliorate its pathogenic effects, we hypothesize that polymorphism of RNQ1 was selected to protect cells from detrimental effects of the [PIN+] prion.

Fig. 1.

Polymorphisms in RNQ1 (Upper) and Rnq1p (Lower) sequences detected in 83 wild S. cerevisiae strains. Polymorphic sites are indicated by base-pair position in RNQ1 and codon in Rnq1p. Insertions are denoted by “ins” after the nucleotides/amino acid(s) flanking the insertion site. Deletions are indicated by “∆” followed by the deleted positions. An asterisk indicates a mutation that was found in only one strain. A indicates that the polymorphism resulted in a premature stop codon.

Fig. 2.

Protein haplotypes for Rnq1p. We used the program DNAsp version 5 to reconstruct haplotype phase. Phase reconstruction was verified in heterozygous individuals using sequences generated from single spores or from cloning reactions. A description of the protein polymorphisms encoded by each haplotype and the frequency (%) in the population are shown.

Fig. P1.

There is a balance between the spread of a nonchromosomal genetic element by outcross mating and the slowing of cell growth as well as loss or gain of the element. Knowing the slowing of cell growth by the 2-μm DNA plasmid, we used this balance to calculate the frequency of outcross mating (∼1% of mitoses). This mating frequency and the known incidence of prions then were used to estimate their detriment to cells, about 1%.