Fitness Trade-Offs Lead to Suppressor Tolerance in Yeast

Genetic variation among individuals within a population provides the raw material for phenotypic diversity upon which natural selection operates. Some given variants can act on multiple standing genomic variations simultaneously and release previously inaccessible phenotypes, leading to increased adaptive potential upon challenging environments. Previously, we identified such a variant related to a tRNA nonsense suppressor in yeast. When introduced into other genetic backgrounds, the suppressor led to an increased population phenotypic variance on various culture conditions, conferring background and environment specific selective advantages. Nonetheless, most isolates are intolerant to the suppressor on rich media due to a severe fitness cost. Here, we found that the tolerance to suppressor is related to a surprising level of fitness outburst, showing a trade-off effect to accommodate the cost of carrying the suppressor. To dissect the genetic basis of such trade-offs, we crossed strains with contrasting tolerance levels on rich media, and analyzed the fitness distribution patterns in the offspring. Combining quantitative tetrad analysis and bulk segregant analysis, we identified two genes, namely MKT1 and RGA1, involved in suppressor tolerance. We showed that alleles from the tolerant parent for both genes conferred a significant gain of fitness, which increased the suppressor tolerance. Our results present a detailed dissection of suppressor tolerance in yeast and provide insights into the molecular basis of trade-offs between fitness and evolutionary potential.