Aspergillus fumigatus versus Genus Aspergillus: Conservation, adaptive evolution and specific virulence genes

Abstract

AbstractAspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be clearly positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory, and virulence related pathways such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal of GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, for antimycotic targeting and understanding fundamental processes of virulence.