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The mating-type determination circuit in  Saccharomyces  yeast serves as a classic paradigm for the genetic control of cell type in all eukaryotes. Using comparative genetics, we discovered a central and conserved, yet previously undetected, component of this genetic circuit: active repression of α-specific genes in a cells. Upon inactivation of the  SUM1  gene in  Saccharomyces bayanus , a close relative of  Saccharomyces cerevisiae , a cells acquired mating characteristics of α cells and displayed autocrine activation of their mating response pathway. Sum1 protein bound to the promoters of α-specific genes, repressing their transcription. In contrast to the standard model, α1 was important but not required for α-specific gene activation and mating of α cells in the absence of Sum1. Neither Sum1 protein expression, nor its association with target promoters was mating-type-regulated. Thus, the α1/Mcm1 coactivators did not overcome repression by occluding Sum1 binding to DNA. Surprisingly, the mating-type regulatory function of Sum1 was conserved in  S. cerevisiae . We suggest that a comprehensive understanding of some genetic pathways may be best attained through the expanded phenotypic space provided by study of those pathways in multiple related organisms.

Interspecies variation reveals a conserved repressor of α-specific genes in Saccharomyces yeasts