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From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution

Kockler, Zachary W., Gordenin, Dmitry A.·2021·Cells
DOI 10.3390/cells10061557PMC PMC8234929

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Abstract

The current SARS-CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS-CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

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  • Analysis of SARS-CoV-2 variants from the database showed higher AC motif mutations (38.3%) than UC motif mutations (31.2%).

    “Interestingly, analysis of SARS-CoV-2 variants from the database also showed higher AC motif mutations (38.3%) than UC motif mutations (31.2%) (Supplementary Fig. S4), as also reported in the previous bioinformatic database analysis3,11,27.”

    From The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness (2022) · cites this paper as [3]

    Section 5.3 describes an analysis of more than 30,000 SARS-CoV-2 genome sequences and reports enrichment of a UC-containing mutation signature. It does not report that AC-motif mutations exceeded UC-motif mutations, or give the cited 38.3% and 31.2% figures. No page number is available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • A high mutation rate of C in AC motif was noted in SARS-CoV-2 and Rubella Virus by prior bioinformatic analysis.

    “A high mutation rate of C in AC motif was also noted in SARS-CoV-2 and Rubella Virus by prior bioinformatic analysis3,11,27.”

    From The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness (2022) · cites this paper as [3]

  • Mutations outside protein-coding ORFs of SARS-CoV-2 were previously designated as non-functional changes.

    “Mutations outside protein-coding ORFs of SARS-CoV-2 were previously designated as non-functional changes3.”

    From The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness (2022) · cites this paper as [3]

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Metadata

Authors
Kockler, Z. W., & Gordenin, D. A.
Affiliations
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of Health, Durham, NC 27709, USA
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-06-20
Volume
10
Issue
6
Pages
1557
ISSN
2073-4409
DOI
10.3390/cells10061557
PMC
PMC8234929
Cited by
26
References
12
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
US National Institute of Health Intramural Research Program (Z1AES103266)

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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