Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

Abstract

Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation.[PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast. P RIONS cause a variety of transmissible spongiform encephalopathies (TSEs) in mammals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and CreutzfeldtJakob disease (CJD) in humans. With all TSEs, endogenous prion protein (PrP) misfolds into an altered, usually proteaseresistant, isoform, termed "PrP res " (" res" for protease resistant). Several prions have been described in fungi (Wickner 1994), with many prion variants of the [PSI+] and [URE3] prions showing toxic or even lethal effects in Saccharomyces cerevisiae (McGlinchey et al. 2011). The [PSI+] prion of S. cerevisiae is formed from the cytosolic protein Sup35p. There are three distinct regions of Sup35p: a glutamine/ asparagine-rich N-terminal domain (amino acids 1-123) that is necessary and sufficient for prion formation (TerAvanesyan et al. 1994) and that facilitates deadenylation and decay of messenger RNA (Hosoda et al. 2003); a middle M domain (amino acids 124-253) of unknown function; and an essential C-terminal domain that functions during translation termination (reviewed by Wickner et al. 2004 (Derkatch et ...

Prions are affected by evolution at two levels

“…The existence of a substantial fraction of wild isolates carrying the [PIN+] prion made possible another line of investigation to distinguish spread by non-mendelian inheritance from selection based on advantage to the host [101]. If [PIN+] is mildly disadvantageous, but is found in the wild simply because it spreads by mating, [PIN+] strains should be enriched in heterozygous wild strains (compared to homozygotes) since these are formed by outcross mating.…”

“…If [PIN+] is mildly disadvantageous, but is found in the wild simply because it spreads by mating, [PIN+] strains should be enriched in heterozygous wild strains (compared to homozygotes) since these are formed by outcross mating. Indeed, 80% of [PIN+] strains were heterozygous for ‘public’ alleles, indicating their arising from outcross matings, whereas only 45% of [pin-] strains had such heterozygosities [101]. These results argue that [PIN+] spreading is largely due to the frequency of outcross mating.…”

Yeast and Fungal Prions

“…For [PINþ], two possible scenarios were considered: (1) there may be some part of the ecological niche of S. cerevisiae in which [PINþ], should it arise, would be beneficial to its host, and this has led to expansion of the line in which it arose because of this benefit; and (2) [PINþ] is mildly detrimental in all niches, but it has spread by mating despite this detriment. Detailed examination of the occasional wild [PINþ] strains has shown that the presence of [PINþ] is associated with the recent occurrence of outcross mating, as shown by heterozygosity (Kelly et al 2014). This result favors the second explanation.…”

Yeast Prions: Structure, Biology, and Prion-Handling Systems

“…The mitochondrial genome began as a bacterial invader and is now nearly universal in eukaryotes because it is beneficial and non-Mendelian (infectious in the same way that yeast prions are infectious). Likewise, the [Het-s] prion is found in Ͼ95% of wild het-s strains of Podospora anserina (138 [PINϩ] showed that they were enriched for strains with evidence of outcross mating, suggesting the latter scenario (143).…”