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

Nature. 2004 Sep 9;431(7005):184-7. doi: 10.1038/nature02885. Epub 2004 Aug 15.


Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI(+)], may exert a profound effect on both. [PSI(+)] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup35p, 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 backgrounds. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Evolution
  • Cell Division
  • Codon, Nonsense / genetics
  • Crosses, Genetic
  • Gene Expression Regulation, Fungal*
  • Genetic Variation / genetics*
  • Genotype
  • Models, Genetic
  • Peptide Termination Factors
  • Phenotype
  • Prions / chemistry
  • Prions / genetics*
  • Prions / metabolism*
  • Protein Biosynthesis / genetics*
  • Protein Conformation
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Codon, Nonsense
  • Peptide Termination Factors
  • Prions
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins