Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nature (Impact Factor: 41.46). 02/2012; 482(7385):363-8. DOI: 10.1038/nature10875
Source: PubMed


The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments and the evolution of new traits. However, this hypothesis is highly controversial. Prions that create new traits have not been found in wild strains, leading to the perception that they are rare 'diseases' of laboratory cultivation. Here we biochemically test approximately 700 wild strains of Saccharomyces for [PSI(+)] or [MOT3(+)], and find these prions in many. They conferred diverse phenotypes that were frequently beneficial under selective conditions. Simple meiotic re-assortment of the variation harboured within a strain readily fixed one such trait, making it robust and prion-independent. Finally, we genetically screened for unknown prion elements. Fully one-third of wild strains harboured them. These, too, created diverse, often beneficial phenotypes. Thus, prions broadly govern heritable traits in nature, in a manner that could profoundly expand adaptive opportunities.

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Available from: Alex K Lancaster
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    • "The ancestor of the prion protein Rnq1p appeared in the same evolutionary epoch. Rnq1p is one of three mostly Q-rich prions that arose within Saccharomycetes, whose[PIN+]/[RNQ+]prion is required for the induction in wild strains of the[PSI+]prion made from Q-rich Sup35p[40,53]. All originally Q-rich prion/PAF sequences arose before the last common ancestor of the Saccharomycetes, either within Ascomycota, or further back in fungal evolution (Fig. 2). "
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    ABSTRACT: Background Prions are transmissible, propagating alternative states of proteins, and are usually made from the fibrillar, beta-sheet-rich assemblies termed amyloid. Prions in the budding yeast Saccharomyces cerevisiae propagate heritable phenotypes, uncover hidden genetic variation, function in large-scale gene regulation, and can act like diseases. Almost all these amyloid prions have asparagine/glutamine-rich (N/Q–rich) domains. Other proteins, that we term here ‘prionogenic amyloid formers’ (PAFs), have been shown to form amyloid in vivo, and to have N/Q-rich domains that can propagate heritable states in yeast cells. Also, there are >200 other S.cerevisiae proteins with prion-like N/Q-rich sequence composition. Furthermore, human proteins with such N/Q-rich composition have been linked to the pathomechanisms of neurodegenerative amyloid diseases. Results Here, we exploit the increasing abundance of complete fungal genomes to examine the ancestry of prions/PAFs and other N/Q-rich proteins across the fungal kingdom. We find distinct evolutionary behavior for Q-rich and N-rich prions/PAFs; those of ancient ancestry (outside the budding yeasts, Saccharomycetes) are Q-rich, whereas N-rich cases arose early in Saccharomycetes evolution. This emergence of N-rich prion/PAFs is linked to a large-scale emergence of N-rich proteins during Saccharomycetes evolution, with Saccharomycetes showing a distinctive trend for population sizes of prion-like proteins that sets them apart from all the other fungi. Conversely, some clades, e.g. Eurotiales, have much fewer N/Q-rich proteins, and in some cases likely lose them en masse, perhaps due to greater amyloid intolerance, although they contain relatively more non-N/Q-rich predicted prions. We find that recent mutational tendencies arising during Saccharomycetes evolution (i.e., increased numbers of N residues and a tendency to form more poly-N tracts), contributed to the expansion/development of the prion phenomenon. Variation in these mutational tendencies in Saccharomycetes is correlated with the population sizes of prion-like proteins, thus implying that selection pressures on N/Q-rich protein sequences against amyloidogenesis are not generally maintained in budding yeasts. Conclusions These results help to delineate further the limits and origins of N/Q-rich prions, and provide insight as a case study of the evolution of compositionally-defined protein domains. Electronic supplementary material The online version of this article (doi:10.1186/s12862-016-0594-3) contains supplementary material, which is available to authorized users.
    Full-text · Article · Dec 2016 · BMC Evolutionary Biology
    • "Wickner, 1994 ). Sup35 is particularly well studied: aggregation blocks its activity as a transcription termination factor and is generally detrimental to the organism (McGlinchey et al., 2011) but may be advantageous in certain environmental situations (Halfmann et al., 2012; Holmes et al., 2013b; True and Lindquist, 2000; True et al., 2004). Like PrP, Sup35 prions form strains with distinct strengths, or degrees of aggregation (Tanaka et al., 2004 ). "
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    ABSTRACT: Prions derived from the prion protein (PrP) were first characterized as infectious agents that transmit pathology between individuals. However, the majority of cases of neurodegeneration caused by PrP prions occur sporadically. Proteins that self-assemble as cross-beta sheet amyloids are a defining pathological feature of infectious prion disorders and all major age-associated neurodegenerative diseases. In fact, multiple non-infectious proteins exhibit properties of template-driven self-assembly that are strikingly similar to PrP. Evidence suggests that like PrP, many proteins form aggregates that propagate between cells and convert cognate monomer into ordered assemblies. We now recognize that numerous proteins assemble into macromolecular complexes as part of normal physiology, some of which are self-amplifying. This review highlights similarities among infectious and non-infectious neurodegenerative diseases associated with prions, emphasizing the normal and pathogenic roles of higher-order protein assemblies. We propose that studies of the structural and cellular biology of pathological versus physiological aggregates will be mutually informative.
    No preview · Article · Feb 2016 · Neuron
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    • "Whether the other four strains initially acquired the trait via [GAR + ] (and were subsequently subject to genetic fixation) or whether they acquired it via other means cannot currently be determined. In any case, like the prions [PSI + ], [RNQ + ], and [MOT3 + ] (Halfmann et al., 2012), [GAR + ] is found in wild yeasts. [GAR + "
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    ABSTRACT: Jarosz and Lancaster are co-first authors [ GAR <sup>+</sup>] is a protein-based element of inheritance that allows yeast ( Saccharomyces cerevisiae ) to circumvent a hallmark of their biology: extreme metabolic specialization for glucose fermentation. When glucose is present, yeast will not use other carbon sources. [ GAR <sup>+</sup>] allows cells to circumvent this textquotedblleftglucose repression.textquotedblright [ GAR <sup>+</sup>] is induced in yeast by a factor secreted by bacteria inhabiting their environment. We report that de novo rates of [ GAR <sup>+</sup>] appearance correlate with the yeasttextquoterights ecological niche. Evolutionarily distant fungi possess similar epigenetic elements that are also induced by bacteria. As expected for a mechanism whose adaptive value originates from the selective pressures of life in biological communities, the ability of bacteria to induce [ GAR <sup>+</sup>] and the ability of yeast to respond to bacterial signals have been extinguished repeatedly during the extended monoculture of domestication. Thus, [ GAR <sup>+</sup>] is a broadly conserved adaptive strategy that links environmental and social cues to heritable changes in metabolism.
    Full-text · Article · Aug 2014 · Cell
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