The prevalent RNA modification on SARS-CoV-2 RNAs may confound the SNP profile and evolutionary patterns revealed by previous studies

Abstract Background The recent outbreak of SARS-CoV-2 has caused severe damage to the world. The concomitant papers on the evolutionary patterns of SARS-CoV-2 is continuously emerging. Studies has utilized the publically available RNA-seq data to find out the so-called SNPs in the virus genome and analyzed their selection patterns. Methods We downloaded a set of RNA-seq data and performed a well-established but modified variant calling pipeline to allow the identification of multiple clustered mutations. Results We found prevalent “putative” but reliably detected A-to-G RNA modifications in the RNA-seq data of SARS-CoV-2 with high signal to noise ratios, presumably caused by the host’s deamination enzymes. Importantly, since SARS-CoV-2 is an RNA virus, it is technically impossible to truly distinguish SNPs and RNA modifications from the RNA-seq data alone. Conclusions The technically indistinguishable RNA modifications and SNPs of SARS-CoV-2 have complicated the situation where many researchers intend to unveil the evolutionary patterns behind the mutation spectrum. This is not a problem for DNA organisms but should be seriously considered when we are investigating the RNA viruses.