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

Mukhtar Sadykov, Tobias Mourier, Qingtian Guan, View ORCID ProfileArnab Pain
doi: https://doi.org/10.1101/2020.06.19.161687
Mukhtar Sadykov
1King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, 23955-6900, Saudi Arabia
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Tobias Mourier
1King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, 23955-6900, Saudi Arabia
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Qingtian Guan
1King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, 23955-6900, Saudi Arabia
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Arnab Pain
1King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, 23955-6900, Saudi Arabia
2Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE); Hokkaido University, N20 W10 Kita-ku, Sapporo, 001-0020 Japan
3Nuffield Division of Clinical Laboratory Sciences (NDCLS), University of Oxford, Headington, Oxford, OX3 9DU, United Kingdom
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  • ORCID record for Arnab Pain
  • For correspondence: arnab.pain@kaust.edu.sa
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Abstract

RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanisms are still largely unknown. In an attempt to address this we used a rapidly growing genomic dataset of SARS-CoV-2 with relevant metadata information. Remarkably, by simply ordering SARS-CoV-2 genomes by their date of collection, we find a progressive increase of C-to-U substitutions resulting in 5'-UCG-3' motif reduction that in turn have reduced the CpG frequency over just a few months of observation. This is consistent with APOBEC-mediated RNA editing resulting in CpG reduction, thus allowing the virus to escape ZAP-mediated RNA degradation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    C>U
    stands for cytosine to uracil substitution, the same applies to other nucleotide substitutions
    APOBEC
    Apolipoprotein B Editing Complex
    ZAP
    zinc-finger antiviral protein
  • Copyright 
    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-ND 4.0 International license.
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    Posted January 05, 2021.
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    Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction
    Mukhtar Sadykov, Tobias Mourier, Qingtian Guan, Arnab Pain
    bioRxiv 2020.06.19.161687; doi: https://doi.org/10.1101/2020.06.19.161687
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    Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction
    Mukhtar Sadykov, Tobias Mourier, Qingtian Guan, Arnab Pain
    bioRxiv 2020.06.19.161687; doi: https://doi.org/10.1101/2020.06.19.161687

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