Genomic Islands in the Pathogenic Filamentous Fungus Aspergillus fumigatus

Abstract

We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility (het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, which are enriched for pseudogenes, transposons and other repetitive elements. At least 20% of A. fumigatus-specific genes appear to be functional and involved in carbohydrate and chitin catabolism, transport, detoxification, secondary metabolism and other functions that may facilitate the adaptation to heterogeneous environments such as soil or a mammalian host. Contrary to what was suggested previously, their origin cannot be attributed to horizontal gene transfer (HGT), but instead is likely to involve duplication, diversification and differential gene loss (DDL). The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated “gene dumps” and, perhaps, simultaneously, as “gene factories”.

Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum

“…These four nonsyntenic regions also contain numerous repeat elements and 23% of the genome's transposable elements (Supplementary Table 2 online). Similar genomic islands have been found in other fungal genomes 11,13,14 . Almost 30% of the predicted P. chrysogenum proteins lack orthologs in other sequenced fungi.…”

Molecular cloning and functional characterization of two CYP619 cytochrome P450s involved in biosynthesis of patulin in Aspergillus clavatus

“…Recently, the whole genome of the patulin-producing fungus A. clavatus was sequenced by The Institute for Genomic Research (Fedorova et al, 2008). When compared with genome sequences from A. clavatus, genes orthologous to 6msas and idh were found in the A. clavatus genome.…”

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

“…While this is not a model system, it is an important research system and the demonstration of sexuality in the lab (O’Gorman et al 2009) built upon the observation of mating type genes and recombination in a population of wild isolates (Paoletti et al 2005). With an emphasis on pathogenicity (Fedorova et al 2008), drug resistance (Mellado et al 2007; Vermeulen et al 2013), and population genetics (Araujo et al 2010), great strides have been made in understanding the biology of this common environmental fungus . Similarly, plant pathogenic Aspergillus species including A. parasiticus and A. flavus have been the subject of intense study (Yu et al 2008) largely because of their production of toxins in the field and in post-harvest storage (Klich 2007).…”