The Function and Evolution of the Aspergillus Genome

Abstract

The genome is a dynamic system storing the genetic information responsible for the astounding diversity of life and examination of its variability is crucial to understanding the phenotypic differences between and within species. In this dissertation, I combined functional, population genetic and evolutionary genomic experiments to study three major facets of genome evolution and function in the filamentous fungal genus Aspergillus, a group with far reaching effects on human society: (1) the pathogenicity of A. fumigatus, (2) the domestication of A. oryzae and (3) the function and evolution of tandemly repeated DNA. The first portion centers on the in vitro examination of the transcriptional profile of A. fumigatus during its infective “biofilm” like state. This examination revealed widespread up-regulation of genes likely contributing to virulence (e.g. toxin-encoding gene clusters), drug resistance (e.g. transporters) and “biofilm” morphology (e.g. hydrophobins). Additionally, this facet includes a population genetics study of drug resistant and susceptible isolates of A. fumigatus from the Netherlands, where drug resistant isolates first originated. This study provided evidence of varying recombination rates between populations as well as the pattern of dissemination of antifungal resistance. The second theme also includes an examination of the genomic features differentiating A. flavus from its domesticated ecotype A. oryzae used in the production of traditional Japanese foods and beverages such as sake and soy sauce. Examination of the A. oryzae transcriptome and proteome showed several changes likely involved in domestication including reduction in toxicity, superior ability to metabolize starch and functional differences in flavor-associated genes, suggesting that, while plant and animal domestication was driven primarily by genetic alterations in developmental pathways, extensive changes of metabolism dominated microbe domestication. The third and final facet focuses on comparative genomic analyses of tandem repeats in coding and non-coding regions. Examination of coding regions revealed that the presence and copy number of tandem repeats was highly variable within and between species and overrepresented in genes with specific functions key to the fungal lifestyle. In non-coding regions, my study found little evidence supporting the longstanding, yet sparsely tested, hypothesis that tandem repeats are a universal source of rapid phenotypic variation.