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Coronavirus genomes carry the signatures of their habitats

View ORCID ProfileYulong Wei, Jordan R. Silke, Parisa Aris, View ORCID ProfileXuhua Xia
doi: https://doi.org/10.1101/2020.06.13.149591
Yulong Wei
1Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486
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Jordan R. Silke
1Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486
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Parisa Aris
1Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486
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Xuhua Xia
1Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486
2Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada K1H 8M5
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  • For correspondence: xxia@uottawa.ca
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ABSTRACT

Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of COVID-19. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter deaminates C into U residues leading to dysfunctional transcripts. We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas viruses that do not infect tissues with abundant AVPs do not share these sequence hallmarks. In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Furthermore, over four months of SARS-CoV-2 evolutionary history, we observed a marked increase in C to U substitutions in the 5’ UTR and ORF1ab regions. This suggests that the two regions could be under constant C to U deamination by APOBEC3. The evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.

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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 4.0 International license.
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Posted June 13, 2020.
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Coronavirus genomes carry the signatures of their habitats
Yulong Wei, Jordan R. Silke, Parisa Aris, Xuhua Xia
bioRxiv 2020.06.13.149591; doi: https://doi.org/10.1101/2020.06.13.149591
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Coronavirus genomes carry the signatures of their habitats
Yulong Wei, Jordan R. Silke, Parisa Aris, Xuhua Xia
bioRxiv 2020.06.13.149591; doi: https://doi.org/10.1101/2020.06.13.149591

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