Obelisks in Your Gut

A collaboratin team of researchers from Standford, Toronto and Politécnica de Valencia Universities has just published a preprint1 describing the “Obelisks”. No they are not the old tapering Egyptian, Greek and Roman monuments, but a new kind of viroid-like elements dwelling in the human mouth and gut.

Viroids were long thought to be limited to plants, but there is new evidence of viroidlike circular RNA genomes amid databases of sequences from animals, bacteria, and other life forms.

Predicted Obelisk secondary structures depicted as “jupiter” plots. Fig 4. Op. cit.

Here, we describe the “Obelisks,” a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. “Obelisks” share several properties: (i) apparently circular RNA ∼1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the “Oblins”. We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ∼7% of analysed stool metatranscriptomes (29/440) and in ∼50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species (Streptococcus sanguinis) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.

“I think this [work] is one more clear indication that we are still exploring the frontiers of this viral universe,”

i.e.: we haven’t seen anything yet

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(1) Zheludev, Ivan N., Robert C. Edgar, Maria Jose Lopez-Galiano, Marcos de la Peña, Artem Babaian, Ami S. Bhatt, and Andrew Z. Fire. ‘Viroid-like Colonists of Human Microbiomes’. bioRxiv, 21 January 2024. https://doi.org/10.1101/2024.01.20.576352.

Featured Image: Jupiter plot of Obelisk-ɑ

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