Genetic variation of secondary metabolite gene clusters in clinical isolates of cryptic species in the Aspergillus fumigatus complex (section Fumigati )

Abstract

Aspergillus fumigatus is a major human pathogen. Several additional species that are genetically distinct but morphologically identical to A. fumigatus can also cause human infection. These so called "cryptic" species are of increasing worldwide concern due to their clinical occurrence and increased antifungal resistance compared to A. fumigatus. Previous analyses of pathogenicity between closely related species revealed great differences in secondary metabolite gene clusters though genomes were pretty similar, highlighting the high evolution rates of secondary metabolite gene clusters, that may be a contributor to phenotypic differences. The current proposal of Research Internship Abroad - Doctorate (BEPE-DR) at the Rokas Laboratory, Vanderbilt University, supervised by Dr. Antonios Rokas aims to analyze secondary metabolite gene clusters in the genomes of clinical isolates of "cryptic" species in Aspergillus fumigatus complex - Fumigati, including analyses of (i) SNPs and indel polymorphisms, gene content polymorphisms, whole gene cluster loss polymorphisms, whole gene cluster polymorphisms, idiomorphic polymorphisms, and genomic location polymorphisms. An overview of the conservation of secondary metabolite gene clusters will also be presented based on orthology analysis. Characterization of SM gene clusters in the "cryptic" species will greatly improve knowledge about these important pathogenic fungi, and possible relationship between secondary metabolite gene cluster repertoire and phenotype.