Working Paper Concept Paper Version 1 This version is not peer-reviewed

Mutation Profile of Over 4,500 SARS-CoV-2 Isolations Reveals Prevalent Cytosine-to-Uridine Deamination on Viral RNAs

Version 1 : Received: 17 April 2020 / Approved: 19 April 2020 / Online: 19 April 2020 (07:05:58 CEST)

How to cite: Jiang, W. Mutation Profile of Over 4,500 SARS-CoV-2 Isolations Reveals Prevalent Cytosine-to-Uridine Deamination on Viral RNAs. Preprints 2020, 2020040335 Jiang, W. Mutation Profile of Over 4,500 SARS-CoV-2 Isolations Reveals Prevalent Cytosine-to-Uridine Deamination on Viral RNAs. Preprints 2020, 2020040335

Abstract

Aims: The sequencing data of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) are rapidly emerging. The mutation profile across SARS-CoV-2 populations is an important inference of the evolution of coronaviruses. Materials & Methods: With 4,521 lines of SARS-CoV-2, we obtained 3,169 unique point mutation sites in the SARS-CoV-2 genome. We counted the numbers and calculated the MAF (minor allele frequency) of each mutation type. Results: Nearly half of the point mutations are C-T mismatches and 20% are A-G mismatches. The MAF of C-T and A-G mismatches is significantly higher than MAF of other mutation types. Conclusions: The excessive C-T mismatches do not resemble the random mutation profile, and are likely to be explained by the cytosine-to-uridine deamination system in hosts. Not only the population analyses in previous studies are questionable, but also the 17% divergence between SARS-CoV-2 and RaTG13 could be erroneous due to the deamination.

Subject Areas

SARS-CoV-2; 4521 lines; mutations; MAF (minor allele frequency); deamination

Comments (2)

Comment 1
Received: 19 April 2020
Commenter: Li
The commenter has declared there is no conflict of interests.
Comment: Glad to see challenge on "the 17% divergence between SARS-CoV-2 and RaTG13". As far as I know, the 17% divergence is proposed by "Tang et al 2020 National Science Review", a group from Peking University and colleagues. Surely, most virologists disagree with the 17% value. It is certainly erroneous. But I did not see your discussion on this in the main text.
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Response 1 to Comment 1
Received: 20 April 2020
Commenter: Guo
The commenter has declared there is no conflict of interests.
Comment: The 17% divergence is obviously overestimated. Tang et al 2020 paper (https://doi.org/10.1093/nsr/nwaa036), the authors from Peking University are not virologists, maybe they ignored the fact that SARS-CoV-2 is an RNA virus. Tang et al used the algorithms to an unsuitable situation, and got an incorrect result. As mentioned by this author, the deamination rate is much higher than the spontaneous mutation rate for RNA viruses. Undoubtedly, the 17% divergence unnecessarily included many mutation sites derived from deamination. The 17% value does not really reflect the divergence between SARS-CoV-2 and RaTG13.

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