Abstract
Over evolutionary timescales, the logic and pattern of cell-type specific gene expression can remain constant, yet the molecular mechanisms underlying such regulation can drift between alternative forms. Here, we document a new example of this principle in the regulation of the haploid-specific genes in a small clade of fungal species. For most ascomycete fungal species, transcription of these genes is repressed in the a/α cell type by a heterodimer of two homeodomain proteins, Mata1 and Matα2. We show that in the species Lachancea kluyveri, most of the haploid-specific genes are regulated in this way, but repression of one haploid-specific gene (GPA1) requires, in addition to Mata1 and Matα2, a third regulatory protein, Mcm1. Model building, based on x-ray crystal structures of the three proteins, rationalizes the requirement for all three proteins: no single pair of the proteins is optimally arranged, and we show that no single pair can bring about repression. This case study exemplifies the idea that the energy of DNA binding can be "shared out" in different ways and can result in different DNA-binding solutions across different genes-while maintaining the same overall pattern of gene expression.