| Summary: | <i>Aspergillus</i> 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 <i>Aspergillus</i>, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species <i>A. fumigatus.</i> Among single-copy orthologs (SCOs) for <i>A. fumigatus</i> and the closely related species <i>A. fischeri</i>, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. <i>A. fumigatus</i> 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 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 (<i>aspf2</i>), siderophore biosynthesis (<i>sidD</i>), fumarylalanine production (<i>sidE</i>), stress tolerance (<i>atfA</i>) and thermotolerance (<i>sodA</i>). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of <i>A. fumigatus</i> as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of <i>A. fumigatus</i>. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.
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