Coding Tandem Repeats Generate Diversity in Aspergillus fumigatus Genes

Abstract

Genes containing multiple coding mini-and microsatellite repeats are highly dynamic components of genomes. Frequent recombination events within these tandem repeats lead to changes in repeat numbers, which in turn alters the amino acid sequence of the corresponding protein. In bacteria and yeasts, the expansion of such coding repeats in cell wall proteins is associated with alterations in immunogenicity, adhesion, and pathogenesis. We hypothesized that identification of repeat-containing putative cell wall proteins in the human pathogen Aspergillus fumigatus may reveal novel pathogenesis-related elements. Here, we report that the genome of A. fumigatus contains as many as 292 genes with internal repeats. Fourteen of 30 selected genes showed size variation of their repeat-containing regions among 11 clinical A. fumigatus isolates. Four of these genes, Afu3g08990, Afu2g05150 (MP-2), Afu4g09600, and Afu6g14090, encode putative cell wall proteins containing a leader sequence and a glycosylphosphatidylinositol anchor motif. All four genes are expressed and produce variable-size mRNA encoding a discrete number of repeat amino acid units. Their expression was altered during development and in response to cell wall-disrupting agents. Deletion of one of these genes, Afu3g08990, resulted in a phenotype characterized by rapid conidial germination and reduced adherence to extracellular matrix suggestive of an alteration in cell wall characteristics. The Afu3g08990 protein was localized to the cell walls of dormant and germinating conidia. Our findings suggest that a subset of the A. fumigatus cell surface proteins may be hypervariable due to recombination events in their internal tandem repeats. This variation may provide the functional diversity in cell surface antigens which allows rapid adaptation to the environment and/or elusion of the host immune system.

Diversity and Plasticity of the Intracellular Plant Pathogen and Insect Symbiont “Candidatus Liberibacter asiaticus” as Revealed by Hypervariable Prophage Genes with Intragenic Tandem Repeats

“…Potential mechanisms for deletion or insertion of the tandem repeats include slipped-strand mispairing, unequal crossover, rolling-circle or circle excision, and reinsertion occurring during bacterial replication (30,39). This size variation caused by different numbers of tandem repeats provides the opportunity for functional diversity and alterations in phenotypes (20,29,48). Although the functions of hyv I and hyv II genes are unknown, BLASTP analysis using positionspecific iterative basic local alignment search tool (PSI-BLAST) indicated that the repeat region of Hyv I protein shares homology with a leucine-rich repeat protein, cell wallassociated biofilm protein, and a cell surface protein.…”

Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes

“…Approximately 3% of these minisatellites are located in genes that encode potential cell surface proteins. One of these genes (Afu3g08990) was inactivated and the corresponding mutant conidia showed decreased cellular adhesion, although no effect on virulence in a mouse model was detected (279).…”

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

“…Although numerous papers were published recently on the application of several typing techniques to A. fumigatus isolates, only some authors attempted to examine the reproductive mode of A. fumigatus populations and the conclusions drawn by them were controversial (Girardin et al 1994, Fridkin & Jarvis 1996, Lasker 2002, Levdansky et al 2007. In Latin America, there is very little information on these different aspects of the epidemiology of aspergillosis.…”