Prions are a common mechanism for phenotypic inheritance in wild yeasts

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% [PIN+] of S. cerevisiae are parallel in-register β-sheet amyloids of Sup35p, Ure2p, and Rnq1p, respectively (7-10); the [Het-s] prion of P. anserina is a β-helical amyloid of the HET-s protein (11). Sup35p is a subunit of the translation termination factor (12, 13), Ure2p is a regulator of nitrogen catabolism (14), and Rnq1p has no known function (15).The mammalian prions are uniformly lethal but nonetheless are found in wild animals. For example, chronic wasting disease of deer and elk is found in ∼10% of wild deer in parts of Wyoming, Colorado, Illinois, and Wisconsin (16). Evidently, infectious spread outpaces the lethal effects on the animals. The [Het-s] prion of P. anserina is involved in heterokaryon incompatibility, a normal function of that species, and, as a result, ∼80% of wild strains with the appropriate chromosomal genotype carry the [Het-s] (20), a result confirmed by others (21) and which we interpreted as meaning that they are substantially detrimental. Nonetheless, others argue that these prions are beneficial, promoting survival by allowing cells to resist stress (22, 23), although the reported effects were not reproducible with the same strains (24). It is reported further that certain stress conditions increase the frequency of[PSI+] when assayed using a synthetic Sup35p with an elevated prion-forming tendency (25). Here we test these conditions for an effect on prion formation by the wild-type Sup35p.Our argument, that the rare occurrence of an infectious agent in nature implies pathologic effects on the host, relies on outcross mating being a fairly frequent event. Yeast prions spread only by mating (there is no extracellular prion species in the replication cycle), and if outcross mating is extremely rare, then yeast prions could be rare even if their effects on the host were neutral. Yeast spores germinate with mating type either a or α, and a and α spores from the same tetrad may mate (intratetrad or brothersister). The mating-type switching system (homothallism) results in the clone from a single germinated spore becoming a mixture of a and α cells which can mate with each other. These two kinds of "selfing" are unlikely to spread any virus, plasmid, or prion, because probably both mating partners will lack the element, or both will have it. Alternat...

supporting

confidence: 75%

Sex, prions, and plasmids in yeast

Kelly

Shewmaker

Kryndushkin

et al. 2012

“…We propose that protein sequence variation, whether by RNA editing (36), yeast prion protein variants (37), or tuning of translational fidelity represent unique forms of environmental adaptation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance

Javid

Sorrentino

Toosky

et al. 2014

172

210

Errors are inherent in all biological systems. Errors in protein translation are particularly frequent giving rise to a collection of protein quasi-species, the diversity of which will vary according to the error rate. As mistranslation rates rise, these new proteins could produce new phenotypes, although none have been identified to date. Here, we find that mycobacteria substitute glutamate for glutamine and aspartate for asparagine at high rates under specific growth conditions. Increasing the substitution rate results in remarkable phenotypic resistance to rifampicin, whereas decreasing mistranslation produces increased susceptibility to the antibiotic. These phenotypic changes are reflected in differential susceptibility of RNA polymerase to the drug. We propose that altering translational fidelity represents a unique form of environmental adaptation.drug tolerance | persisters

“…Yeast has at least four well-studied sources of inherited, nonchromosomal information: mitochondrial DNA, an endogenous dsRNA virus (16,17), prions (18,19), and a 2μ plasmid (20,21).…”

Section: Genetic Interactions | Extrachromosomal | Nonlinear Modelmentioning

confidence: 99%

Interactions between chromosomal and nonchromosomal elements reveal missing heritability

Edwards

Symbor-Nagrabska

Dollard

et al. 2014

The measurement of any nonchromosomal genetic contribution to the heritability of a trait is often confounded by the inability to control both the chromosomal and nonchromosomal information in a population. We have designed a unique system in yeast where we can control both sources of information so that the phenotype of a single chromosomal polymorphism can be measured in the presence of different cytoplasmic elements. With this system, we have shown that both the source of the mitochondrial genome and the presence or absence of a dsRNA virus influence the phenotype of chromosomal variants that affect the growth of yeast. Moreover, by considering this nonchromosomal information that is passed from parent to offspring and by allowing chromosomal and nonchromosomal information to exhibit nonadditive interactions, we are able to account for much of the heritability of growth traits. Taken together, our results highlight the importance of including all sources of heritable information in genetic studies and suggest a possible avenue of attack for finding additional missing heritability.A fundamental problem in genetics is unraveling the link between genotype and phenotype. Ascertaining the heritability of a trait is a key step toward harnessing the predictive capacity of genetic information for human disease risk assessment and therapy (1). Knowledge of all of the elements contributing to heritability would facilitate the establishment of a causal relationship between the information that is passed down from generation to generation and the resulting phenotype. Genomewide association studies (GWASs) have successfully identified many human polymorphisms that are associated with traits such as height, eye color, or susceptibility to common diseases, but these variants typically explain only a small proportion of the observed heritability of a trait (2, 3).A number of explanations for missing heritability have been suggested (2), including the existence of many weak variants with effects too small to achieve statistical significance (4), interactions between variants that cannot be identified with current studies (5), rare variants that were not identified by GWAS, and epigenetic effects (6-8). The contribution of nonchromosomal information to the missing heritability is rarely considered, despite the fact that there is a long history documenting the effect in many organisms of diverse cytoplasmic elements on phenotype. Recent work on a mouse model of Crohn disease supports a combinatorial model of complex disease traits in which the pathology requires the interaction between a specific mutation in the mouse and a specific strain of virus (9). Another recent study showed strong effects on the plant metabolome stemming from variation in mitochondrial and chloroplast genomes (10). In humans, the importance of nonchromosomal information has been supported by targeted analyses, but these studies have not analyzed its impact on heritability in a well-controlled context (11-13). Such nonchromosomal interactions might help e...