RESUMEN
The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG dinucleotides, nor a link between the activity of ZAP and the low CpG abundance of the SARS-CoV-2 genome.
Asunto(s)
COVID-19/genética , Fosfatos de Dinucleósidos/genética , Genoma Viral/genética , Proteínas de Unión al ARN/genética , SARS-CoV-2/genética , Animales , Secuencia de Bases , Sitios de Unión/genética , COVID-19/virología , Fosfatos de Dinucleósidos/metabolismo , Evolución Molecular , Interacciones Huésped-Patógeno/genética , Humanos , Motivos de Nucleótidos/genética , Unión Proteica , ARN Viral/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , SARS-CoV-2/fisiología , Replicación Viral/genéticaRESUMEN
The outbreak of COVID-19 has brought great threat to human health. Its causative agent is a severe acute respiratory syndrome-related coronavirus which has been officially named SARS-CoV-2. Here we report the discovery of extremely low CG abundance in its open reading frames. We found that CG reduction in SARS-CoV-2 is achieved mainly through mutating C/G into A/T, and CG is the best target for mutation. Meanwhile, 5'-untranslated region of SARS-CoV-2 has high CG content and is capable of forming an internal ribosome entry site (IRES) to recruit host ribosome for translating its RNA. These features allow SARS-CoV-2 to reproduce efficiently in host cells, because less energy is consumed in disrupting the stem-loops formed by its genomic RNA. Notably, genomes of cellular organisms also have very low CG abundance, suggesting that mutating C/G into A/T occurs universally in all life forms. Moreover, CG is the dinucleotide related to CpG island, mutational hotspot and single nucleotide polymorphism in cellular organisms. The relationship between these features is worthy of further investigations.