The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus

Abstract

Filamentous fungi produce diverse secondary metabolites (SMs) essential to their ecology and adaptation. Although each SM is typically produced by only a handful of species, SM production is coordinated with developmental changes by a suite of widely conserved transcriptional regulators. Here, I examined the interplay between the taxonomic narrowness of SM distribution and the broad conservation of global SM and development regulators in four Aspergillus species that include the human pathogen Aspergillus fumigatus and the model organism A. nidulans, producers of medically important SMs including penicillin and gliotoxin. Evolutionary analysis of SM pathways in these four species showed that they are highly divergent, due to changes in both the genomic layout and gene content of SM pathways. RNA sequencing of two transcriptional regulators of SM and development, veA and mtfA, showed that the effects of deletion of each gene on SM pathway regulation were similar in the two species, though the genes and pathways regulated in each species differed. In contrast, the role of these two regulators in development is strikingly different. Whereas veA regulates developmental processes in both species, mtfA regulates development in the self-fertilizing A. nidulans but not in the outcrossing A. fumigatus, despite near total conservation of developmental genes. These results suggest that fungal species have extensively rewired global transcriptional regulators to fit their diverse ecological needs and regulate the rapidly evolving process of secondary metabolite production.