The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2.
CpG motifs
SARS-CoV-2
evolution of synonymous mutations
pathogen-associated molecular patterns
pattern recognition receptors
ssRNA viruses
viral host mimicry
Journal
Molecular biology and evolution
ISSN: 1537-1719
Titre abrégé: Mol Biol Evol
Pays: United States
ID NLM: 8501455
Informations de publication
Date de publication:
19 05 2021
19 05 2021
Historique:
pubmed:
9
2
2021
medline:
1
6
2021
entrez:
8
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33555346
pii: 6130826
doi: 10.1093/molbev/msab036
pmc: PMC7928797
doi:
Substances chimiques
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2428-2445Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : UpdateOf
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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