Intra-genome variability in the dinucleotide composition of SARS-CoV-2
View ORCID ProfilePaul Digard, Hui-Min Lee, Colin Sharp, Finn Grey, View ORCID ProfileEleanor R Gaunt
doi: https://doi.org/10.1101/2020.05.08.083816
Abstract
CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. Artificial modification of CpG frequency is a valid approach for live attenuated vaccine development, and if this is to be applied to SARS-CoV-2, we must first understand the role CpG motifs play in regulating SARS-CoV-2 replication. Accordingly, the CpG composition of the newly emerged SARS-CoV-2 genome was characterised in the context of other coronaviruses. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. Although SARS-CoV-2 exhibits overall strong CpG suppression, this varies considerably across the genome, and the Envelope (E) open reading frame (ORF) and ORF10 demonstrate an absence of CpG suppression.
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