G-quadruplexes in helminth parasites

Abstract

Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.

The Newly Sequenced Genome of Pisum sativum Is Replete with Potential G-Quadruplex-Forming Sequences—Implications for Evolution and Biological Regulation

“…Interestingly, there was no significant drop in PQS density in the P. sativum genome for high G4H scores. This was in contrast with what has been observed in most other species, as previous analyses revealed that most of the PQSs found in Platyhelminthes [ 41 ], Archaea [ 15 ], and bacteria [ 14 ] have a relatively low G4Hunter score, and the number of PQSs in these organisms decreases sharply above a score of 1.6. Strikingly, nuclear DNA and mt- and cpDNA differ not only in PQS frequencies, but also in the localization of these PQSs.…”

Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

“…As expected, the PQS frequency decreased with higher G4Hunter scores. This decreased number of PQS is similar to that of other genomes analyzed so far, with a significant decrease in the count of detected PQS upon the selection of higher thresholds, as found in viruses, , bacteria, archaea, and eukaryotes. , For most genotypes, PQS were present even in categories with G4Hunter scores above 1.8 and 2. However, the most striking decrease in PQS density was observed in HDVs with genotype 3, where we did not find PQS with a G4Hunter score above 1.8.…”

Programmed DNA elimination in the parasitic nematode Ascaris

“…Additionally, no small RNAs or long non-coding RNAs appear to directly mark the break sites or contribute to PDE [ 66 , 69 ]. A recent analysis suggested that G-quadruplex DNA is enriched in extended (10 to 20 kb) regions covering 40 Ascaris CBRs [ 70 ]. However, G-quadruplexes are also enriched in other regions of the Ascaris genome, and many CBRs have no G-quadruplexes [ 70 ], suggesting G-quadruplex DNA is probably not a component of the CBRs.…”