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Comparative Analysis of Pathogenic Aspergillus fumigatus


We acquired from Merck, Inc., the genome sequences of a new clinical isolate, FGSC A1163, of an important human pathogen, Aspergillus fumigatus, and two closely related, but rarely pathogenic species, Neosartorya fischeri NRRL181 and A. clavatus NRRL1. Comparative genomic analysis of FGSC A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable, and unique regions in each genome. While the core regions are 99.8% identical at the nucleotide level, identity over some variable regions can be as low 40%. The most divergent loci include putative heterokaryon incompatibility, (het) genes associated with the non-self recognition and programmed cell death reaction in filamentous fungi. Intriguingly, one predicted het gene is orthologous to rosA encoding a transcriptional regulator of sexual development in A. nidulans, which suggests a link between these two cellular programs.

Further comparison has revealed that A. fumigatus contains isolate- and species-specific genes, which comprise ~2% and 9% of the genome, respectively. These lineage-specific genes differ in variability, dispensability, and size from the core genes and encode accessory functions. Subsequent phylogenetic analysis demonstrated that these genes emerged though duplication, accelerated diversification and/or gene loss. Horizontal gene transfer appears to be a minor contributing factor in this process. Most lineage-specific genes cluster in large chromosomal islands, which display a strong subtelomeric bias, have low gene density, and harbour a disproportionate number of pseudogenes, transposons, and other repetitive elements. These regions may function as designated "gene dumps" and/or as "gene factories" of lineage-specific genes.

Although A. fumigatus was chosen as the primary focus of this study, similar chromosomal structures are observed in the genomes of N. fischeri and A. clavatus, suggesting that all the aspergilli are poised for rapid adaptation to heterogeneous environments such as soil, compost, or a mammalian host.


National Institute of Allergy and Infectious Disease (NIAID)

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