Eukaryotic Cell doi:10.1128/EC.00229-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Coding tandem repeats generate genetic diversity in Aspergillus fumigatus genes
Emma Levdansky,
Jacob Romano,
Yona Shadkchan,
Haim Sharon,
Kevin J. Verstrepen,
Gerald R. Fink,
and
Nir Osherov*
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel. Harvard University FAS Center for Systems Biology, 7 Divinity Ave., Cambridge 02138, MA, USA. Department of Molecular and Microbial Systems, K.U.Leuven, Faculty of Applied Bioscience and Engineering, Kasteelpark Arenberg 22, B-3001 Leuven, Belgium. Whitehead Institute for Biomedical Research/Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts, USA
* To whom correspondence should be addressed. Email:
nosherov{at}post.tau.ac.il.
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Abstract |
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Genes containing multiple coding mini- and microsattelite 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 yeast, 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, Afu3g08990, Afu2g05150 (MP-2), Afu4g09600, and Afu6g14090, encode putative cell-wall proteins containing a leader sequence and a GPI anchor motif. All four genes are expressed and produce size-variable 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 wall of dormant and germinating conidia. Our findings suggest that a subset of the A. fumigatus cell-surface proteins may be hyper-variable 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.
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