A yeast prion provides a mechanism for genetic variation and phenotypic diversity

  title={A yeast prion provides a mechanism for genetic variation and phenotypic diversity},
  author={Heather L. True and Susan Lindquist},
A major enigma in evolutionary biology is that new forms or functions often require the concerted effects of several independent genetic changes. It is unclear how such changes might accumulate when they are likely to be deleterious individually and be lost by selective pressure. The Saccharomyces cerevisiae prion [PSI+] is an epigenetic modifier of the fidelity of translation termination, but its impact on yeast biology has been unclear. Here we show that [PSI+] provides the means to uncover… 
Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits
[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.
Prion Switching in Response to Environmental Stress
The hypothesis that [PSI+] is a mechanism to increase survival in fluctuating environments and might function as a capacitor to promote evolvability is supported.
Prions are a common mechanism for phenotypic inheritance in wild yeasts
Biochemically test approximately 700 wild strains of Saccharomyces for [PSI+] or [MOT3+], and find these prions in many, and they conferred diverse phenotypes that were frequently beneficial under selective conditions.
Prion-mediated diversity in yeast
  • Rowley
  • Biology
    Trends in genetics : TIG
  • 2000
Does the central dogma still stand?
There is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology.
Prions as protein-based genetic elements.
The ability to become a prion appears to be evolutionarily conserved in two cases, and [PSI(+)] provides a mechanism for genetic variation and phenotypic diversity in response to changing environments.
It is found that evolvability is a more likely explanation, as long as environmental change makes partial read-through of stop codons adaptive at a frequency of at least once every million years.
Epigenetic regulation of genome integrity by a prion-based mechanism
[MPH1+] provides resistance to DNA damage, a gain-of-function trait that requires helicase activity and interactions with other DNA repair proteins, and fuels a quasi-Lamarckian form of inheritance that promotes survival of the current generation and diversification of the next.


[PSI+]: an epigenetic modulator of translation termination efficiency.
The series of experiments supporting the yeast prion hypothesis are reviewed and another look is provided at the 30 years of work preceding this theory in light of the current state of knowledge.
Hsp90 as a capacitor for morphological evolution
It is reported that when Drosophila Hsp90 is mutant or pharmacologically impaired, phenotypic variation affecting nearly any adult structure is produced, with specific variants depending on the genetic background and occurring both in laboratory strains and in wild populations.
Support for the Prion Hypothesis for Inheritance of a Phenotypic Trait in Yeast
A cytoplasmically inherited genetic element in yeast, [PSI+], was confirmed to be a prionlike aggregate of the cellular protein Sup35 by differential centrifugation analysis and microscopic
Oligopeptide-repeat expansions modulate ‘protein-only’ inheritance in yeast
It is shown that replacing the wild-type SUP35 gene with a repeat-expansion mutation induces new [PSI +] elements, the first mutation of its type among these newly described elements of inheritance.
Role of cryptic genes in microbial evolution.
It is proposed that cryptic genes persist as a vital element of the genetic repertoire, ready for recall by mutational activation in future generations, indicating that powerful and biologically important mechanisms exist to prevent the loss of cryptic genes.
Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae.
It is hypothesized that in addition to the [PSI+] prion-determining domain in the Sup35p N-terminus, there is another self-propagating conformational determinant in the C-proximal part of Sup 35p and that this second prion is responsible for the Pin+ phenotype.
Molecular Basis of a Yeast Prion Species Barrier
Translation termination efficiency can be regulated in Saccharomyces cerevisiae by environmental stress through a prion‐mediated mechanism
It is demonstrated that [PSI+] strains do exhibit enhanced tolerance to heat and chemical stress, compared with [psi−] strains, and it is shown that the prion‐like determinant [PSi+] is able to regulate translation termination efficiency in response to environmental stress.
Isolation and characterization of omnipotent suppressors in the yeast Saccharomyces cerevisiae.
Differences between alleles of the same locus and similarities between allele of different loci suggest that the omnipotent suppressors encode proteins that effect different functions and that altered forms of each of the proteins can effect the same function.
Agents that cause a high frequency of genetic change from [psi+] to [psi-] in Saccharomyces cerevisiae.
In this study, the following agents have been shown to induce the same genetic change: guanidine hydrochloride at 1 mM, dimethyl sulfoxide at 2.5% v/v and ethanol or methanol at 10% v-v.