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Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

Sadykov, Mukhtar, Mourier, Tobias, Guan, Qingtian, Pain, Arnab·2021·Journal of Molecular Cell Biology

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Crossref · 10.1093/jmcb/mjab011

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Figure 1 APOBEC-driven C>U substitutions in the SARS-CoV-2 genome contribute to CpG loss allowing viral RNA to escape from ZAP-mediated viral RNA destruction. (A) Single nucleotide variation events observed between individual SARS-CoV-2 sample sequences (n = 22164) and the reference genome. (B) The number of C>U substitutions across sample dates. The average number of substitutions for each sampling day is plotted (blue line, left y-axis) with ±standard deviation (SD) as error bars. The number of samples for each day is shown as red bars (right y-axis). (C) Folding potential of positions with C>U changes (Supplementary Text). P-values from Fisher’s exact test are shown above bars. N.S., non-significant. (D) The fraction of [A/C/G/U]CG triplets that are changed to [A/C/G/U]UG over time. The average fractions, relative to the reference genome, are shown as circles for each sampling day (x-axis). Error bars denote ±SD. Only dates with at least 20 samples are plotted. (E) A model for the consequences of host-driven evolution by APOBEC enzymes on viral CpG dinucleotide composition.
Figure 1 APOBEC-driven C>U substitutions in the SARS-CoV-2 genome contribute to CpG loss allowing viral RNA to escape from ZAP-mediated viral RNA destruction. (A) Single nucleotide variation events observed between individual SARS-CoV-2 sample sequences (n = 22164) and the reference genome. (B) The number of C>U substitutions across sample dates. The average number of substitutions for each sampling day is plotted (blue line, left y-axis) with ±standard deviation (SD) as error bars. The number of samples for each day is shown as red bars (right y-axis). (C) Folding potential of positions with C>U changes (Supplementary Text). P-values from Fisher’s exact test are shown above bars. N.S., non-significant. (D) The fraction of [A/C/G/U]CG triplets that are changed to [A/C/G/U]UG over time. The average fractions, relative to the reference genome, are shown as circles for each sampling day (x-axis). Error bars denote ±SD. Only dates with at least 20 samples are plotted. (E) A model for the consequences of host-driven evolution by APOBEC enzymes on viral CpG dinucleotide composition.CC BY · PubMed Central

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Research works printed but not linked: 11

  1. Blanc, 2010, APOBEC-1-mediated RNA editing, Wiley Interdiscip. Rev. Syst. Biol. Med, 2, 594, 10.1002/wsbm.82 · DOI
  2. Blanco-Melo, 2020, Imbalanced host response to SARS-CoV-2 drives development of COVID-19, Cell, 181, 1036, 10.1016/j.cell.2020.04.026 · DOI · Paper page
  3. Digard, 2020, Intra-genome variability in the dinucleotide composition of SARS-CoV-2, Virus Evol, 6, veaa057, 10.1093/ve/veaa057 · DOI
  4. Di Giorgio, 2020, Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2, Sci. Adv., 6, eabb5813, 10.1126/sciadv.abb5813 · DOI · Paper page
  5. Luo, 2020, Molecular mechanism of RNA recognition by zinc-finger antiviral protein, Cell Rep, 30, 46, 10.1016/j.celrep.2019.11.116 · DOI
  6. McDaniel, 2020, Deamination hotspots among APOBEC3 family members are defined by both target site sequence context and ssDNA secondary structure, Nucleic Acids Res, 48, 1353, 10.1093/nar/gkz1164 · DOI
  7. Rice, 2020, Evidence for strong mutation bias toward, and selection against, U content in SARS-CoV-2: implications for vaccine design, Mol. Biol. Evol, 38, 67, 10.1093/molbev/msaa188 · DOI
  8. Salter, 2018, Modeling the embrace of a mutator: APOBEC selection of nucleic acid ligands, Trends Biochem. Sci, 43, 606, 10.1016/j.tibs.2018.04.013 · DOI
  9. Schmidt, 2021, The SARS-CoV-2 RNA–protein interactome in infected human cells, Nat. Microbiol. 6, 339–353., 10.1038/s41564-020-00846-z · DOI · Paper page
  10. Simmonds, 2020, Rampant C→U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses: causes and consequences for their short- and long-term evolutionary trajectories, mSphere, 5, e00408, 10.1128/mSphere.00408-20 · DOI · Paper page
  11. Wei, 2020, Coronavirus genomes carry the signatures of their habitats, PLoS One, 10.1371/journal.pone.0244025 · DOI

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Metadata

Authors
Sadykov, M., Mourier, T., Guan, Q., & Pain, A.
Affiliations
King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah 23955-6900, Saudi Arabia
Venue
Journal of Molecular Cell Biology
Published
2021-02-25
Volume
13
Issue
3
Pages
225-227
ISSN
1759-4685
Cited by
15
References
2
Language
en

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