Prions are a common mechanism for phenotypic inheritance in wild yeasts

Abstract

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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Figure 1: Identification and verification of prions in wild yeast.
Figure 2: Prion-contingent phenotypes of [ PSI + ] isolates.
Figure 3: Genetic assimilation of the [ PSI + ]-dependent adhesive phenotype in meiotic progeny of UCD978.
Figure 4: Prions of the cell wall-remodelling transcription factor, Mot3, have diverse phenotypic consequences in wild strains.
Figure 5: The curable Hsp104-dependent epigenetic elements in wild yeast can be cytoplasmically transferred.

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Acknowledgements

We are grateful to L. Bisson and L. Joseph, who provided the Department of Viticulture and Enology yeast collection from the University of California, Davis, USA. We also received strains from G. Fink, E. Louis, F. Dietrich and S. Dietzmann, and L. Kruglyak. We thank M. Taipale, K. Allendoerfer, K. Matlack, L. Pepper, V. Khurana, G. Fink, L. Joseph, A. Hochwagen and G. Walker for materials, discussions, and/or critical reading of the manuscript. N. Azubuine and T. Nanchung provided a constant supply of plates and media. S.L. is a Howard Hughes Medical Institute (HHMI) investigator. This work was supported by grants from the G. Harold and Leila Y. Mathers Foundation and HHMI. D.F.J. was supported as an HHMI fellow of the Damon Runyon Cancer Research Foundation (DRG-1964-08) and by an NIH Pathway to independence award (K99 GM098600). S.K.J. was supported as a summer research student by the Howard Hughes Medical Institute (HHMI) Exceptional Research Opportunities Program (EXROP).

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R.H., D.F.J., A.K.L. and S.L. designed the experiments. R.H. performed SDD–AGE analyses. R.H., D.F.J., S.K.J. and A.C. carried out phenotyping experiments. D.F.J. analysed high-throughput phenotyping data. D.F.J. and A.K.L. analysed whole-genome sequence data. D.F.J. and A.C. performed cytoductions. R.H., D.F.J. and S.L. wrote the paper.

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Correspondence to Susan Lindquist.

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Halfmann, R., Jarosz, D., Jones, S. et al. Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482, 363–368 (2012). https://doi.org/10.1038/nature10875

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