Evidence for Sexuality in the Opportunistic Fungal Pathogen Aspergillus fumigatus

Abstract

Aspergillus fumigatus is a medically important opportunistic pathogen and a major cause of respiratory allergy. The species has long been considered an asexual organism. However, genome analysis has revealed the presence of genes associated with sexual reproduction, including a MAT-2 high-mobility group mating-type gene and genes for pheromone production and detection (Galagan et al., personal communication; Nierman et al., personal communication). We now demonstrate that A. fumigatus has other key characteristics of a sexual species. We reveal the existence of isolates containing a complementary MAT-1 alpha box mating-type gene and show that the MAT locus has an idiomorph structure characteristic of heterothallic (obligate sexual outbreeding) fungi. Analysis of 290 worldwide clinical and environmental isolates with a multiplex-PCR assay revealed the presence of MAT1-1 and MAT1-2 genotypes in similar proportions (43% and 57%, respectively). Further population genetic analyses provided evidence of recombination across a global sampling and within North American and European subpopulations. We also show that mating-type, pheromone-precursor, and pheromone-receptor genes are expressed during mycelial growth. These results indicate that A. fumigatus has a recent evolutionary history of sexual recombination and might have the potential for sexual reproduction. The possible presence of a sexual cycle is highly significant for the population biology and disease management of the species.

Population structure and diversity of the pathogenic fungus Aspergillus fumigatus isolated from different sources and geographic origins

“…These findings reaffirm the hypothesis that variability is due to an ancient recombination and some selective pressure (Varga 2003). These hypotheses are reinforced by the work of Paoletti et al (2005), which shows that A. fumigatus isolates containing the complementary alpha-domain MAT gene were identified, and showed the expression of MAT1-1 and MAT1-2 and of genes encoding for sex pheromones and pheromone receptors. These results indicate that A. fumigatus has a recent evolutionary history of sexual recombination and might have the potential for sexual reproduction.…”

Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

“…mat-1 and pheromone-precursor and receptor genes were not expressed during fed-batch fermentation, but this was not surprising given that mating and pheromone signaling require specific environmental conditions for induction (Supplementary Table 7 online). It has recently been suggested that the 'asexual' species, A. fumigatus and A. oryzae might have sexual potential 9,18 . A similar situation could apply to A. niger, which would be of great value for strain improvement.…”

Eukaryotic microbes, species recognition and the geographic limits of species: examples from the kingdom Fungi

“…In addition, Pö ggeler (2002), Dyer et al (2003) and Paoletti et al (2005) found that the genes known to be required for mating in fungi that can reproduce sexually in cultivation are also found in A. fumigatus. Furthermore, Paoletti et al (2005) showed that A. fumigatus individuals of each of the two mating types were found in equal proportion throughout the range of the species. Therefore, not only is A. fumigatus a single global species, but it also appears to reproduce by recombination as well as clonal means.…”