Molecular genetic analysis of mating type gene function and sexual reproduction in Aspergillus nidulans

The mating type genes at the mat loci represent master regulators of fungal sexual reproduction. Mat loci encode transcription factors with conserved motifs, alpha-box and/or HMG-box domains, which coordinate the expression of sex-specific genes. The genetic organization and developmental regulation of the mat genes are key determinants of sexual identity and determine reproductive behaviour; either homothallic (self-fertile) or heterothallic (cross-fertile). Molecular function of mating type genes and mechanisms underlying regulation of fungal sexual reproduction are not well understood. In this study I am using the homothallic fungus, Aspergillus nidulans (An) as a model system to investigate the regulation, molecular function, structural and functional conservation of fungal HMG box sex determining factors.;Gene deletion/complementation studies and analysis of the transcriptional regulation of An matA (HMG) revealed that matA encodes a critical modulator of sexual morphogenesis and is required for fruiting body and ascospore differentiation. Progressive up-regulation of the matA expression during sexual development controls the fruiting body development and ascospore formation. The transcriptional expression of matA might be driven from downstream promoter elements and is tightly regulated by upstream repressor elements. Duplication of the matA gene in the haploid genome of An triggers premeiotic, homology dependent gene silencing (HDGS). Silencing affects both endogenous and transgene matA alleles and is induced by transcriptional activity of the ectopically integrated transgene.;The lack of an experimentally amenable sexual genetic system in Aspergillus fumigatus (Af) is a major limitation in the study of its human pathogenesis. Using interspecies gene exchange between Af and An, I have demonstrated that Af Mat1-2 is a structural and functional homolog of the An MatA transcription factor capable of regulating the An sexual cycle.;Furthermore, I have investigated the structural and functional relatedness between An MatA and human SRY, sex determining factors. The HMG box of fungal matA shares high level of the amino acid conservation with the HMG box of human SRY. Functional studies suggest that SRY expressed in An under the matA promoter could be involved in the regulation of fungal sexual development. Collectively, presented studies provide novel insights into the genetic regulation of eukaryotic sexual reproduction.