The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 Journal Article


Authors: Di Gioacchino, A.; Šulc, P.; Komarova, A. V.; Greenbaum, B. D.; Monasson, R.; Cocco, S.
Article Title: The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2
Abstract: COVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We characterize CpG content by a CpG force that accounts for statistical constraints acting on the genome at the nucleotidic and amino acid levels. The CpG force, as the CpG content, is overall low compared with other pathogenic betacoronaviruses; however, it widely fluctuates along the genome, with a particularly low value, comparable with the circulating seasonal HKU1, in the spike coding region and a greater value, comparable with SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3'UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the zinc finger antiviral protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition-transversion bias, and the pressure to lower CpG content. © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Keywords: genetics; evolution, molecular; molecular evolution; virus rna; cpg island; cpg islands; pathogenicity; virus genome; rna, viral; genome, viral; cpg motifs; humans; human; covid-19; sars-cov-2; evolution of synonymous mutations; pathogen-associated molecular patterns; pattern recognition receptors; ssrna viruses; viral host mimicry
Journal Title: Molecular Biology and Evolution
Volume: 38
Issue: 6
ISSN: 0737-4038
Publisher: Oxford University Press  
Date Published: 2021-06-01
Start Page: 2428
End Page: 2445
Language: English
DOI: 10.1093/molbev/msab036
PUBMED: 33555346
PROVIDER: scopus
PMCID: PMC7928797
DOI/URL:
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
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