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Viroid-like colonists of human microbiomes

View ORCID ProfileIvan N. Zheludev, View ORCID ProfileRobert C. Edgar, View ORCID ProfileMaria Jose Lopez-Galiano, View ORCID ProfileMarcos de la Peña, View ORCID ProfileArtem Babaian, View ORCID ProfileAmi S. Bhatt, View ORCID ProfileAndrew Z. Fire
doi: https://doi.org/10.1101/2024.01.20.576352
Ivan N. Zheludev
1Stanford University, Department of Biochemistry, Stanford, CA, USA
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  • For correspondence: zheludev@stanford.edu afire@stanford.edu
Robert C. Edgar
2Corte Madera, CA, USA
Roles: Independent researcher
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Maria Jose Lopez-Galiano
3Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia–CSIC, Valencia, Spain
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Marcos de la Peña
3Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia–CSIC, Valencia, Spain
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Artem Babaian
4University of Toronto, Department of Molecular Genetics, Ontario, Canada
5University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Ontario, Canada
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Ami S. Bhatt
6Stanford University, Department of Genetics, Stanford, CA, USA
7Stanford University, Department of Medicine, Division of Hematology, Stanford, CA, USA
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Andrew Z. Fire
6Stanford University, Department of Genetics, Stanford, CA, USA
8Stanford University, Department of Pathology, Stanford, CA, USA
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  • For correspondence: zheludev@stanford.edu afire@stanford.edu
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://purl.stanford.edu/wb363nt3637

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted January 21, 2024.
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Viroid-like colonists of human microbiomes
Ivan N. Zheludev, Robert C. Edgar, Maria Jose Lopez-Galiano, Marcos de la Peña, Artem Babaian, Ami S. Bhatt, Andrew Z. Fire
bioRxiv 2024.01.20.576352; doi: https://doi.org/10.1101/2024.01.20.576352
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Viroid-like colonists of human microbiomes
Ivan N. Zheludev, Robert C. Edgar, Maria Jose Lopez-Galiano, Marcos de la Peña, Artem Babaian, Ami S. Bhatt, Andrew Z. Fire
bioRxiv 2024.01.20.576352; doi: https://doi.org/10.1101/2024.01.20.576352

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