Tracing the Origin of the Fungal alpha 1 Domain Places Its Ancestor in the HMG-Box Superfamily: Implication for Fungal Mating-Type Evolution

Background: Fungal mating types in self-incompatible Pezizomycotina are specified by one of two alternate sequences occupying the same locus on corresponding chromosomes. One sequence is characterized by a gene encoding an HMG protein, while the hallmark of the other is a gene encoding a protein with an alpha 1 domain showing similarity to the M protein of Saccharomyces cerevisiae. DNA-binding HMG proteins are ubiquitous and well characterized. In contrast, alpha 1 domain proteins have limited distribution and their evolutionary origin is obscure, precluding a complete understanding of mating-type evolution in Ascomycota. Although much work has focused on the role of the S. cerevisiae Mat alpha 1p protein as a transcription factor, it has not yet been placed in any of the large families of sequence-specific DNA-binding proteins.Methodology/Principal Findings: We present sequence comparisons, phylogenetic analyses, and in silico predictions of secondary and tertiary structures, which support our hypothesis that the alpha 1 domain is related to the HMG domain. We have also characterized a new conserved motif in alpha 1 proteins of Pezizomycotina. This motif is immediately adjacent to and downstream of the alpha 1 domain and consists of a core sequence Y-[LMIF]-x(3)-G-[WL] embedded in a larger conserved motif.Conclusions/Significance: Our data suggest that extant alpha 1-box genes originated from an ancestral HMG gene, which confirms the current model of mating-type evolution within the fungal kingdom. We propose to incorporate alpha 1 proteins in a new subclass of HMG proteins termed MAT alpha_ HMG.