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% [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...

Dictyostelium discoideum has a highly Q/N-rich proteome and shows an unusual resilience to protein aggregation

“…7). Amyloids have also been identified in lower eukaryotes such as the budding yeast Saccharomyces cerevisiae, where they have been proposed to be pathological (8,9). This, however, is controversial, and others have suggested that S. cerevisiae may use amyloids to generate phenotypic diversity, thus allowing it to adapt to environmental stress (10,11).…”

Amyloid cannot resist identification

“…In support of this hypothesis, it was reported that severe stress conditions increased the rate of de novo [PSI+] generation, 25 although we could not independently confirm this observation. 28 If this hypothesis is true, prions should arise and be stabilized under stress conditions. TAPI offers an opportunity to test whether yeast strains subjected to selective pressures could generate specific SDS-resistant protein profiles.…”

Sporadic Distribution of Prion-Forming Ability of Sup35p from Yeasts and Fungi

“…While beneficial phenotypes of [PSI+] formation have been reported (Eaglestone et al 1999;True et al 2004), they have not been reproducible (True et al 2004;Namy et al 2008), even using the identical strains. Moreover, the common occurrence of lethal and near-lethal variants of [PSI+] (McGlinchey et al 2011) and the rare occurrence of [PSI+] in the wild (Chernoff et al 2000;Resende et al 2003;Nakayashiki et al 2005;Halfmann et al 2012) implies that [PSI+] is generally detrimental to its host (Nakayashiki et al 2005;Masel and Griswold 2009;Kelly et al 2012).…”