Haploinsufficiency of the sex-determining genes at MATα restricts genome expansion in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, mating type of haploid cells is determined by the presence or absence of the MATα idiotype containing MATα1 and MATα2, which encode the transcription factors. These proteins are characterized by rapid turnover, but the physiological relevance of this property remains unclear. Here, we show a direct link between their intracellular levels and sexual stability. Polyploid cells with fewer MATα copies had unstable sexual phenotypes, causing morphological changes and an increase in cell death; these effects were mediated by hyperactivation of the mating pheromone response pathway. Thus, the MATα1 and MATα2 genes are haploinsufficient genes, and the reduction in their product levels causes sex fluctuation. Chromosome III harboring the mating type locus is the most prone to loss in diploids. We propose that the haploinsufficiency of MATα compensates for the drop-out prone nature of chromosome III, thereby suppressing speciation through increased genome size via polyploidization.