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. 2009 Mar;181(3):1057-63.
doi: 10.1534/genetics.108.100297. Epub 2009 Jan 19.

The strength of selection against the yeast prion [PSI+]

Joanna Masel  1 , Cortland K Griswold
Affiliations

The strength of selection against the yeast prion [PSI+]

Joanna Masel et al. Genetics. 2009 Mar.

Abstract

The [PSI(+)] prion causes widespread readthrough translation and is rare in natural populations of Saccharomyces, despite the fact that sex is expected to cause it to spread. Using the recently estimated rate of Saccharomyces outcrossing, we calculate the strength of selection necessary to maintain [PSI(+)] at levels low enough to be compatible with data. Using the best available parameter estimates, we find selection against [PSI(+)] to be significant. Inference regarding selection on modifiers of [PSI(+)] appearance depends on obtaining more precise and accurate estimates of the product of yeast effective population size N(e) and the spontaneous rate of [PSI(+)] appearance m. The ability to form [PSI(+)] has persisted in yeast over a long period of evolutionary time, despite a diversity of modifiers that could abolish it. If mN(e) < 1, this may be explained by insufficiently strong selection. If mN(e) > 1, then selection should favor the spread of [PSI(+)] resistance modifiers. In this case, rare conditions where [PSI(+)] is adaptive may permit its persistence in the face of negative selection.

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Figures

F<sc>igure</sc> 1.—
Figure 1.—
Logical breakdown of all possible scenarios of direct and indirect selection on [PSI+], together with an assessment of their plausibility in explaining the data. [PSI+] must be adaptive, neutral, or deleterious under the majority of normal conditions found in the wild, as shown by the three direct selection possibilities on the left. If direct negative selection against [PSI+] is appreciable, the next question is whether indirect selection against modifiers of [PSI+] is also appreciable. Appreciable selection is equivalent to the standard population genetics criterion sNe > 1. Conditions for appreciable selection being compatible with data on [PSI+] rarity are derived in terms of the spontaneous rates of [PSI+] appearance m and disappearance formula image, as well as the frequency ɛ of [PSI+] within a [PIN+] population and the effective population size in the wild Ne. The conditions under which each scenario is compatible with data are summarized along each branch.
F<sc>igure</sc> 2.—
Figure 2.—
Strength of selection against [PSI+] vs. the rate of spontaneous [PSI+] loss formula image: (A) formula image and (B) formula image. Tsai et al. (2008) estimates of the probabilities of sex, automixis, amphimixis, and haplo-selfing are assumed. Above the dotted line the strength of selection is >1/Ne, where Ne = 5 × 106. The vertical dotted line corresponds to Tank et al.'s (2007) upper limit on formula image (formula image is constrained to fall to the left of this line).
F<sc>igure</sc> 3.—
Figure 3.—
Strength of selection against the modifier allele prf+ vs. the rate of spontaneous [PSI+] loss formula image. The dotted lines and conditions are the same as in Figure 2.
F<sc>igure</sc> 4.—
Figure 4.—
The solid and dashed curves give the boundaries between nearly neutral (top) and deleterious (bottom) parameter regions for [PSI+] and prf+, respectively, based on Ne = 5 × 106. [PSI+] is deleterious while its modifier prf+ is nearly neutral only in the very restricted shaded region in the middle for both formula image and formula image. The horizontal dotted line corresponds to Tank et al.'s (2007) upper limit on formula image (formula image is constrained to fall below this line).
See this image and copyright information in PMC

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