Fungal infections cause >1 million deaths annually and the emergence of antifungal resistance has prompted the exploration for novel antifungal targets. Quadruplexes are four-stranded nucleic acid secondary structures, which can regulate processes such as transcription, translation, replication and recombination. They are also found in genes linked to virulence in microbes, and ligands that bind to quadruplexes can eliminate drug-resistant pathogens. Using a computational approach, we quantified putative quadruplex-forming sequences (PQS) in 1359 genomes across the fungal kingdom and explored their presence in genes related to virulence, drug resistance and biological processes associated with pathogenicity in Aspergillus fumigatus. Here we present the largest analysis of PQS in fungi and identify significant heterogeneity of these sequences throughout phyla, genera and species. PQS were genetically conserved in Aspergillus spp. and frequently pathogenic species appeared to contain fewer PQS than their lesser/non-pathogenic counterparts. GO-term analysis identified that PQS-containing genes were involved in processes linked with virulence such as zinc ion binding, the biosynthesis of secondary metabolites and regulation of transcription in A. fumigatus. Although the genome frequency of PQS was lower in A. fumigatus, PQS could be found enriched in genes involved in virulence, and genes upregulated during germination and hypoxia. Moreover, PQS were found in genes involved in drug resistance. Quadruplexes could have important roles within fungal biology and virulence, but their roles require further elucidation.

• Klíčová slova
• Aspergillus fumigatus, Fungi, G-quadruplexes, drug resistance, i-motifs, in-silico, virulence,
• MeSH
• algoritmy MeSH
• antifungální látky farmakologie   MeSH
• Ascomycota MeSH
• Aspergillus fumigatus genetika   MeSH
• Aspergillus MeSH
• fungální léková rezistence účinky léků   MeSH
• genom fungální účinky léků   MeSH
• genom virový MeSH
• transkriptom MeSH
• virulence MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• antifungální látky MeSH

The importance of unusual DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, G-quadruplexes (G4s) have gained in popularity during the last decade, and their presence and functional relevance at the DNA and RNA level has been demonstrated in a number of viral, bacterial, and eukaryotic genomes, including humans. Here, we performed the first systematic search of G4-forming sequences in all archaeal genomes available in the NCBI database. In this article, we investigate the presence and locations of G-quadruplex forming sequences using the G4Hunter algorithm. G-quadruplex-prone sequences were identified in all archaeal species, with highly significant differences in frequency, from 0.037 to 15.31 potential quadruplex sequences per kb. While G4 forming sequences were extremely abundant in Hadesarchaea archeon (strikingly, more than 50% of the Hadesarchaea archaeon isolate WYZ-LMO6 genome is a potential part of a G4-motif), they were very rare in the Parvarchaeota phylum. The presence of G-quadruplex forming sequences does not follow a random distribution with an over-representation in non-coding RNA, suggesting possible roles for ncRNA regulation. These data illustrate the unique and non-random localization of G-quadruplexes in Archaea.

• Klíčová slova
• Archaea, G4-forming motif, genome analysis, sequence prediction, unusual nucleic acid structures,
• MeSH
• Archaea klasifikace   genetika   metabolismus   MeSH
• archeální proteiny genetika   metabolismus   MeSH
• cirkulární dichroismus MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• DNA chemie   genetika   metabolismus   MeSH
• druhová specificita MeSH
• fylogeneze MeSH
• G-kvadruplexy * MeSH
• genom archeí genetika   MeSH
• genomika metody   MeSH
• konformace nukleové kyseliny MeSH
• RNA chemie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• archeální proteiny MeSH
• DNA vazebné proteiny MeSH
• DNA MeSH
• RNA MeSH