Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 184 (2), 393-400

The Spontaneous Appearance Rate of the Yeast Prion [PSI+] and Its Implications for the Evolution of the Evolvability Properties of the [PSI+] System

Affiliations

The Spontaneous Appearance Rate of the Yeast Prion [PSI+] and Its Implications for the Evolution of the Evolvability Properties of the [PSI+] System

Alex K Lancaster et al. Genetics.

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.

Figures

F<sc>igure</sc> 1.—
Figure 1.—
Comparison between the three possible modes ([PSI+], genetic mimic, point mutation revertant) of the expression of 3′-UTR sequences in yeast. (a) The normal [psi−] phenotypic state; (b) the [PSI+] prion causes readthrough and low-level expression of 3′-UTRs across multiple genes, appearing at rate mPSI; (c) a genetic mimic of [PSI+] such as the sal3-4 mutant of Sup35 (Eaglestone et al. 1999) appearing at rate mmimic not reversible by the application of guanidine hydrochloride; (d) a point mutation in a single stop codon at rate μpoint, leading to incorporation of formerly 3′-UTR into a single coding sequence. (e) [PSI+] can act as a “stop-gap” mechanism, buying a lineage more time to acquire one or more adaptive stop codon readthrough point mutations. When this genetic assimilation is complete, [PSI+] can revert to [psi−] (Masel and Bergman 2003; Griswold and Masel 2009).
F<sc>igure</sc> 2.—
Figure 2.—
The model of Lancaster and Masel (2009) predicts the parameter range (shaded) for which mPSI (expressed as a function of the elevation from the unstressed baseline observed value of 5.8 × 10−7) is compatible with both a 95% C.I. of mmimic of (2.04–2.77) × 10−6 and Ne = (3–6) × 106. The upper bound is given by the combination {mmimic = 2.04 × 10−6, Ne = 6 × 106} and the lower bound by {mmimic = 2.77 × 10−6, Ne = 3 × 106}.
F<sc>igure</sc> 3.—
Figure 3.—
Sensitivity of our inference to the effective population size, Ne. For Ne ∼ 5 × 106, as estimated for Saccharomyces, we infer a role for natural selection in favoring [PSI+]-mediated evolvability if and only if mPSI is elevated by stress, as has been observed. (a) For Ne ≲ 105 we would not infer evolvability, even with realistically elevated switching rates. (b) Selection for evolvability would be inferred even in the absence of stress-mediated induction for Ne ≳ 4 × 107. Higher values of Ne are not shown because their computation requires excessive memory, but the result is still clear.
F<sc>igure</sc> 3.—
Figure 3.—
Sensitivity of our inference to the effective population size, Ne. For Ne ∼ 5 × 106, as estimated for Saccharomyces, we infer a role for natural selection in favoring [PSI+]-mediated evolvability if and only if mPSI is elevated by stress, as has been observed. (a) For Ne ≲ 105 we would not infer evolvability, even with realistically elevated switching rates. (b) Selection for evolvability would be inferred even in the absence of stress-mediated induction for Ne ≳ 4 × 107. Higher values of Ne are not shown because their computation requires excessive memory, but the result is still clear.

Similar articles

See all similar articles

Cited by 52 articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback