title: The spontaneous appearance rate of the yeast prion [PSI+] and its implications for the evolution of the evolvability properties of the [PSI+] system.
abstract: Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects of natural selection on modifiers of [PSI+] appearance have been the subject of much debate. It seems likely that [PSI+] would be at least mildly deleterious in most environments, but this may be counteracted by its evolvability properties on rare occasions. Indirect selection on modifiers of [PSI+] is predicted to depend primarily on the spontaneous [PSI+] appearance rate, but this critical parameter has not previously been adequately measured. Here we measure this epimutation rate accurately and precisely as 5.8 x 10(-7) per generation, using a fluctuation test. We also determine that genetic "mimics" of [PSI+] account for up to 80% of all phenotypes involving general nonsense suppression. Using previously developed mathematical models, we can now infer that even in the absence of opportunities for adaptation, modifiers of [PSI+] are only weakly deleterious relative to genetic drift. If we assume that the spontaneous [PSI+] appearance rate is at its evolutionary optimum, then opportunities for adaptation are inferred to be rare, such that the [PSI+] system is favored only very weakly overall. But when we account for the observed increase in the [PSI+] appearance rate in response to stress, we infer much higher overall selection in favor of [PSI+] modifiers, suggesting that [PSI+]-forming ability may be a consequence of selection for evolvability.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Lancaster
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Bardill
authors.forename: Heather L
authors.initials: HL
authors.lastname: True
authors.forename: Joanna
authors.initials: J
authors.lastname: Masel
mesh_terms: D018388:Codon, Terminator / Q000235:genetics; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D011328:Prions / Q000235:genetics*; D012440:Saccharomyces / Q000235:genetics; D012641:Selection, Genetic; D015003:Yeasts / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D005656:Fungal Proteins; D011328:Prions