High natural prevalence of a fungal prion

Abstract

Prions are infectious proteins that cause fatal diseases in mammals. Prions have also been found in fungi, but studies on their role in nature are scarce. The proposed biological function of fungal prions is debated and varies from detrimental to benign or even beneficial. [Het-s] is a prion of the fungus Podospora anserina. The het-s locus exists as two antagonistic alleles that constitute an allorecognition system: the het-s allele encoding the protein variant capable of prion formation and the het-S allele encoding a protein variant that cannot form a prion. We document here that het-s alleles, capable of prion formation, are nearly twice as frequent as het-S alleles in a natural population of 112 individuals. Then, we report a 92% prevalence of [Het-s] prion infection among the het-s isolates and find evidence of the role of the [Het-s]/het-S allorecognition system on the incidence of infection by a deleterious senescence plasmid. We explain the het-s/het-S allele ratios by the existence of two selective forces operating at different levels. We propose that during the somatic stage, the role of [Het-s]/HET-S in allorecognition leads to frequency-dependent selection for which an equilibrated frequency would be optimal. However, in the sexual cycle, the [Hets] prion causes meiotic drive favoring the het-s allele. Our findings indicate that [Het-s] is a selected and, therefore, widespread prion whose activity as selfish genetic element is counteracted by balancing selection for allorecognition polymorphism.heterokaryon incompatibility | self/nonself recognition | spore killing

Prion-like Nanofibrils of Small Molecules (PriSM) Selectively Inhibit Cancer Cells by Impeding Cytoskeleton Dynamics

“…Although the prion form and the monomeric form of TIA-1 have different functions (formation of stress granules by the prion TIA-1 and posttranscriptional regulator of gene expression by the monomeric TIA-1) (8), the only biologically active species of cytoplasmic polyadenylation element-binding protein and mitochondrial antiviral signaling protein, intriguingly, are their prion-like forms. Moreover, many non-pathogenic prions also exist in fungi (9), such as yeast (10) and Podospora anserine (11). Interestingly, protein aggregates formed by mixing with fatty acid (HAMLET) also exhibit beneficial function (12,13).…”

Yeast and Fungal Prions

“…Accordingly, amyloid of HETs made in vitro has a uniform structure, reflected in sharp peaks in solid-state NMR studies (Wasmer et al 2008). This functional prion is found in .90% of wild isolates with the het-s allele, as expected for a beneficial prion (Debets et al 2012 (Chernoff et al 2000;Resende et al 2003;Nakayashiki et al 2005;Halfmann et al 2012), both implying that they are pathological. Reports of marginal benefits of carrying the mildest [PSIþ] prion variants (Eaglestone et al 1999;True and Lindquist 2000;Halfmann et al 2012) have not been reproduced (True and Lindquist 2000;Namy et al 2008;Wickner et al 2015).…”

On the evolutionary trajectories of signal-transducing amyloids in fungi and beyond

“…9 As might be expected for a functional prion, [Het-s] is extremely abundant in wild populations of P. anserina. It thus appears that functional amyloids not only carry a variety of molecular functions, but are also found in particularly distant taxa.…”