Interspecies Genomic Variation and Transcriptional Activeness of Secondary Metabolism-Related Genes in Aspergillus Section Fumigati

Abstract

Filamentous fungi produce various bioactive compounds that are biosynthesized by sets of proteins encoded in biosynthesis gene clusters (BGCs). For an unknown reason, many BGCs are transcriptionally silent in laboratory conditions, which has hampered the discovery of novel fungal compounds. The transcriptional reactiveness of fungal secondary metabolism is not fully understood. To gain the comprehensive view, we conducted comparative genomic and transcriptomic analyses of nine closely-related species of Aspergillus section Fumigati (A. fumigatus, A. fumigatiaffinis, A. novofumigatus, A. thermomutatus, A. viridinutans, A. pseudoviridinutans, A. lentulus, A. udagawae, and Neosartorya fischeri). For expanding our knowledge, we newly sequenced genomes of A. viridinutans and A. pseudoviridinutans, and reassembled and reannotated the previously released genomes of A. lentulus and A. udagawae. Between 34 and 84 secondary metabolite (SM) backbone genes were identified in the genomes of these nine respective species, with 8.7–51.2% being unique to the species. A total of 247 SM backbone gene types were identified in the nine fungi. Ten BGCs are shared by all nine species. Transcriptomic analysis using A. fumigatus, A. lentulus, A. udagawae, A. viridinutans, and N. fischeri was conducted to compare expression levels of all SM backbone genes in four different culture conditions; 32–83% of SM backbone genes in these species were not expressed in the tested conditions, which reconfirmed that large part of fungal SM genes are hard to be expressed. The species-unique SM genes of the five species were expressed with lower frequency (18.8% in total) than the SM genes that are conserved in all five species (56%). These results suggest that the expression tendency of BGCs is correlated with their interspecies distribution pattern. Our findings increase understanding of the evolutionary processes associated with the regulation of fungal secondary metabolism.

Extensive Non-Coding Sequence Divergence Between the Major Human Pathogen Aspergillus fumigatus and its Relatives

“…A major outstanding question emanating from our work is whether this extensive non-coding sequence variation of closely related Aspergillus species that vary in their pathogenicity functionally contributes to differences in gene expression between strains and species. Currently, there are no datasets available that report genome-wide differential expression data for A. fumigatus and close relatives; to our knowledge, the only published differential expression study of A. fumigatus and close relatives focused on expression differences only for genes involved in secondary metabolism (Takahashi et al, 2021). Designing and performing differential gene expression experiments in diverse Aspergillus species will be a future aim.…”

“…In fungi, non-coding regions found immediately upstream of genes' protein-coding regions are bound by transcription factors (TFs), impact transcriptional activity (Kim et al, 2019), and play roles in vital biological processes such as zinc homeostasis (Eide, 2020) and thermotolerance (Yamamoto et al, 2008). Differences in gene expression have become an important focus in understanding A. fumigatus virulence (Chung et al, 2014;de Castro et al, 2014;Furukawa et al, 2020;Ries et al, 2020;Takahashi et al, 2021;Colabardini et al, 2022). However, the role non-coding regions play in differential gene regulation between A. fumigatus and close relatives remains largely unknown.…”

Genomic insights into Aspergillus sydowii 29R-4-F02: unraveling adaptive mechanisms in subseafloor coal-bearing sediment environments

“…In addition, we assembled the mitochondrial genome of strain 29R-4-F02, which has a length of 26,185 bp and contains 13 genes, including 7 NADH–ubiquinone oxidoreductase genes, 3 cytochrome c oxidase genes, 1 cytochrome b gene, 1 ribosomal protein gene, and 1 ATP synthase gene, with a GC content of 23.67%. The size and number of genes in the mitochondrial genome of strain 29R-4-F02 are similar to those of other Aspergillus species, with genome sizes ranging from 27,817 to 77,649 bp and gene numbers ranging from 14 to 21 ( Zhao et al, 2012 ; Takahashi et al, 2021 ; Jing et al, 2022 ).…”

Intimate genetic relationships and fungicide resistance in multiple strains of Aspergillus fumigatus isolated from a plant bulb

“…The annotation of assembled nuclear genomes was performed by the Funannotate pipeline (ver. 1.7.4) ( https://funannotate.readthedocs.io/en/latest/ ) as described previously (Takahashi et al ., 2021 ). Following identification of repeat sequences by RepeatModeler (ver.…”