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Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits

Nature volume 431, pages 184–187 (2004)Cite this article

Abstract

Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits1,2,3, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI+], may exert a profound effect on both4. [PSI+] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup35p5, and is transmitted from mother to progeny. Curing cells of [PSI+] alters their survival in different growth conditions and produces a spectrum of phenotypes in different genetic backgrounds4. Here we show, by examining three plausible explanations for this phenotypic diversity, that all traits tested involved [PSI+]-mediated read-through of nonsense codons. Notably, the phenotypes analysed were genetically complex, and genetic re-assortment frequently converted [PSI+]-dependent phenotypes to stable traits that persisted in the absence of [PSI+]. Thus, [PSI+] provides a temporary survival advantage under diverse conditions, increasing the likelihood that new traits will become fixed by subsequent genetic change. As an epigenetic mechanism that globally affects the relationship between genotype and phenotype, [PSI+] expands the conceptual framework for phenotypic plasticity, provides a one-step mechanism for the acquisition of complex traits and affords a route to the genetic assimilation of initially transient epigenetic traits.

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Figure 1: [PSI+]-related phenotypes are dependent on read-through.
Figure 2: Variable strength phenotypes are observed with progeny from outcrosses.
Figure 3: Progeny from an outcross of 5V-H19 show [PSI+]-independent caffeine resistance.

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Acknowledgements

We thank members of the Lindquist lab, the True lab, R. Parker and J. Masel for discussions and comments on experiments and the manuscript. We thank J. Weissman, S. Liebman and their lab members for plasmids and strains. This research was supported by the National Institutes of Health.

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  1. Heather L. True

    Present address: Department of Cell Biology and Physiology, Washington University Medical School, St Louis, Missouri, 63130, USA

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, 02142, USA

    Heather L. True, Ilana Berlin & Susan L. Lindquist

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  1. Heather L. True
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Correspondence to Susan L. Lindquist.

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Supplementary information

Supplementary Figures 1 and 3 (PPT 277 kb)

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Supplementary Information

Supplementary results, discussion, tables and supplementary figure 2 legend. (DOC 169 kb)

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True, H., Berlin, I. & Lindquist, S. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431, 184–187 (2004). https://doi.org/10.1038/nature02885

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