G-quadruplex occurrence and conservation: more than just a question of guanine–cytosine content

Abstract

G-quadruplexes are motifs found in DNA and RNA that can fold into tertiary structures. Until now, they have been studied experimentally mainly in humans and a few other species. Recently, predictions have been made with bacterial and archaeal genomes. Nevertheless, a global comparison of predicted G4s (pG4s) across and within the three living kingdoms has not been addressed. In this study, we aimed to predict G4s in genes and transcripts of all kingdoms of living organisms and investigated the differences in their distributions. The relation of the predictions with GC content was studied. It appears that GC content is not the only parameter impacting G4 predictions and abundance. The distribution of pG4 densities varies depending on the class of transcripts and the group of species. Indeed, we have observed that, in coding transcripts, there are more predicted G4s than expected for eukaryotes but not for archaea and bacteria, while in noncoding transcripts, there are as many or fewer predicted G4s in all species groups. We even noticed that some species with the same GC content presented different pG4 profiles. For instance, Leishmania major and Chlamydomonas reinhardtii both have 60% of GC content, but the former has a pG4 density of 0.07 and the latter 1.16.

Analysis of G-Quadruplex-Forming Sequences in Drought Stress-Responsive Genes, and Synthesis Genes of Phenolic Compounds in Arabidopsis thaliana

“…Although such large-scale predictions are computationally extensive, it would be beneficial to also inspect other higher plants in the future to see if this trend (frequency of PQS in nuclear DNA < frequency of PQS in plastid DNA < frequency of PQS in mitochondrial DNA) is always the same. These data should then be correlated with GC content as well because generally higher GC content may favor more PQS, although recently it was shown that genomes with a very similar GC content may differ significantly in their PQS frequencies [ 27 ]. Considering nuclear and plastid genomes which have very similar GC content in Arabidopsis thaliana, an explanation for different PQS frequencies may be found in significantly different gene densities.…”

GAIA: G-quadruplexes in alive creature database

“…When the database is accessed, a default query is automatically made and outputted. This default query is made in order to retrieve all G4s predicted in Escherichia coli (Ecol) ( 16 ). The default query can always be made again by accessing the ‘Home’ page.…”

“…The number of pG4s in all species and their location/transcript classes are presented in Table 1 . The number of pG4s is higher in eukaryotes because G4s are more predicted than expected by chance (for more details on the method, see ( 16 )), but also because there are more annotated eukaryotic transcripts. Indeed, over all eukaryotes, there is an average of 2 transcripts per gene (for humans, the average go up to 4), while only 1 transcript per gene is annotated for both archaea and bacteria.…”

“…The locations most altered by the annotation are the introns in bacteria and archaea because they are less common in both of these kingdoms, and the UTRs because only CDS are annotated. For a more detailed analysis of the pG4s distribution, see ( 16 ).…”

Editorial: Biology of non-canonical nucleic acids from humans to pathogens

“…The recent research that focused on G4s and microorganisms worked to set up or implement specific tools to predict their presence in the genome of pathogens (Lavezzo et al, 2018 ; Cagirici et al, 2022 ; Vannutelli et al, 2022 ), as G-rich regions cannot be straightforwardly coupled to the possible folding of G4s. Moreover, the pandemic years we have been through have brought to light the importance of promptly understanding if G4s are embedded in the pathogen's or influence the host-pathogen interaction network, or if they represent feasible antiviral targets.…”