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 gt; 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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