Abstract

Aspergillus 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 us 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 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 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 an 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, antimycotic targeting and understanding fundamental virulence processes.

Highlights

  • Introduction1.5 to 2 million deaths each year, which exceeds the global mortality estimates for both malaria and tuberculosis [1]

  • Fungal diseases and, invasive fungal infections lead to an estimated1.5 to 2 million deaths each year, which exceeds the global mortality estimates for both malaria and tuberculosis [1]

  • We found that all the thirteen gliotoxin gene cluster genes are conserved in all six sequenced A. fumigatus strains and are single-copy orthologs except gliA, which had two paralogs in each strain (Table 2)

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Summary

Introduction

1.5 to 2 million deaths each year, which exceeds the global mortality estimates for both malaria and tuberculosis [1]. During 200 million years of evolution, Aspergilli developed as a group of ubiquitous fungi [2]. Among the known Aspergilli, the environmentally acquired pathogen Aspergillus fumigatus is the predominant, ubiquitous, opportunistic. Microorganisms 2021, 9, 2014 pathogenic species causing life-threatening invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA) in immunodeficient patients, as well as allergic disease in immunoreactive patients. The conidia of A. fumigatus released from the conidiophores are dispersed in the environment and remain dormant until encountering the environmental conditions that allow metabolic activation. The inhalation of conidia, fungal growth and tissue invasion in immunocompromised patients can result in the establishment of invasive disease and represents a major cause of morbidity and mortality

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