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Updated: May 18, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Sex, prions, and plasmids in yeast
Amy C Kelly1, Frank P Shewmaker, Dmitry Kryndushkin
1Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Insights
Yeast prions like [PIN+] can spread through mating, even if they cause harm. Genetic diversity in yeast, particularly in the RNQ1 gene, likely evolved to protect against these infectious protein elements.
Area of Science:
- Molecular biology
- Genetics
- Prion biology
Background:
- Prions are infectious proteins that can cause disease.
- Yeast prions, such as [PSI+], [URE3], and [PIN+], are self-propagating protein aggregates.
- The prevalence and spread of prions in natural populations are not fully understood.
Purpose of the Study:
- To investigate the prevalence of yeast prions in wild yeast strains.
- To understand the mechanisms of prion transmission and their impact on host fitness.
- To explore the role of genetic variation in prion resistance.
Main Methods:
- Screening of 70 wild yeast strains for the presence of [PSI+], [URE3], and [PIN+] prions.
- Estimation of outcross mating frequency using 2-μm DNA plasmid carriage and heterozygosity at the RNQ1 locus.
- Analysis of RNQ1 polymorphisms, including premature stop codons and sequence variations, for their effect on [PIN+] propagation.
Main Results:
- The [PIN+] prion was found in approximately 16% of wild yeast strains, while [PSI+] and [URE3] were not detected.
- The detriment of carrying [PSI+], [URE3], or [PIN+] was estimated to be greater than 1%.
- RNQ1 polymorphisms, including those that prevent [PIN+] propagation or create a transmission barrier, were identified. Strains carrying [PIN+] were more likely to be heterozygous at RNQ1, suggesting sexual transmission.
Conclusions:
- The [PIN+] prion is present in natural yeast populations and spreads via mating.
- Genetic polymorphism in the RNQ1 gene likely provides a defense mechanism against the detrimental effects of the [PIN+] prion.
- Natural selection may favor RNQ1 variants that confer resistance to prion infection.
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