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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    • "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.
    Cell 08/2014; 158:1072-1082. DOI:10.1016/j.cell.2014.07.024 · 32.24 Impact Factor
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    • "We recently demonstrated that prions formed by diverse yeast proteins have adaptive value. They are widespread in ecologically diverse wild strains of yeast (Halfmann et al., 2012). Moreover, they change the capacity of cells to utilize a vast array of different nutrients and to survive many stressful environments (True and Lindquist, 2000; True et al., 2004; Halfmann et al., 2012; Suzuki et al., 2012). "
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    ABSTRACT: In experimental science, organisms are usually studied in isolation, but in the wild, they compete and cooperate in complex communities. We report a system for cross-kingdom communication by which bacteria heritably transform yeast metabolism. An ancient biological circuit blocks yeast from using other carbon sources in the presence of glucose. [ GAR <sup>+</sup>], a protein-based epigenetic element, allows yeast to circumvent this textquotedblleftglucose repressiontextquotedblright and use multiple carbon sources in the presence of glucose. Some bacteria secrete a chemical factor that induces [ GAR <sup>+</sup>]. [ GAR <sup>+</sup>] is advantageous to bacteria because yeast cells make less ethanol and is advantageous to yeast because their growth and long-term viability is improved in complex carbon sources. This cross-kingdom communication is broadly conserved, providing a compelling argument for its adaptive value. By heritably transforming growth and survival strategies in response to the selective pressures of life in a biological community, [ GAR <sup>+</sup>] presents a unique example of Lamarckian inheritance.
    Cell 08/2014; 158:1083-1093. DOI:10.1016/j.cell.2014.07.025 · 32.24 Impact Factor
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    • "Whereas a gain of function is associated with formation of CPEB prion in brain, most yeast prion phenotypes reflect partial functional inactivation of prion-forming proteins due to aggregation. This has fueled a long-term debate on whether most prions are diseases, egoistic elements, or functional components of the cell (True and Lindquist, 2000; Halfmann et al., 2012; Kelly et al., 2012; Newby and Lindquist, 2013; Wickner et al., 2013). "
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    ABSTRACT: Tia1/Pub1 is a stress granule component carrying a Q/N-rich prion domain. We provide direct evidence that Tia1 forms a prion in yeast. Moreover, Tia1/Pub1 acts cooperatively with release factor Sup35/eRF3 to establish a two-protein self-propagating state. This two-protein prion driven by the Q/N-rich prion domains of Sup35 and Tia1/Pub1 can be visualized as distinctive line structures along tubulin cytoskeleton. Furthermore, we find that tubulin-associated complex containing Pub1 and Sup35 oligomers normally exists in yeast, and its assembly depends on prion domains of Pub1 and Sup35. This Sup35/Pub1 complex, which also contains TUB1 mRNA and components of translation machinery, is important for the integrity of the tubulin cytoskeleton: PUB1 disruption and Sup35 depletion from the complex lead to cytoskeletal defects. We propose that the complex is implicated in protein synthesis at the site of microtubule assembly. Thus our study identifies the role for prion domains in the assembly of multiprotein complexes.
    Molecular Cell 06/2014; 55(2). DOI:10.1016/j.molcel.2014.05.027 · 14.02 Impact Factor
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