Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2
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Abstract
To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.
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SciScore for 10.1101/2020.03.11.987222: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: This study was undertaken as part of the national disease outbreak and the response and the protocols were approved by the ethics committee of the National Healthcare Group. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Material from clinical samples was used to inoculate Vero-E6 cells (ATCC®CRL-1586™). Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Ethics statement: This study was undertaken as part of the national disease outbreak and the response and … SciScore for 10.1101/2020.03.11.987222: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: This study was undertaken as part of the national disease outbreak and the response and the protocols were approved by the ethics committee of the National Healthcare Group. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Material from clinical samples was used to inoculate Vero-E6 cells (ATCC®CRL-1586™). Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Ethics statement: This study was undertaken as part of the national disease outbreak and the response and the protocols were approved by the ethics committee of the National Healthcare Group. National Healthcaresuggested: NonePatient samples were collected under PROTECT (2012/00917), a multi-centred Prospective Study to Detect Novel Pathogens and Characterize Emerging Infections. PROTECTsuggested: (ProTECT, RRID:SCR_004531)Raw NGS reads were trimmed by Trimmomatic v0.39 [19] to remove adaptors and low-quality bases. Trimmomaticsuggested: (Trimmomatic, RRID:SCR_011848)Genome sequences were assembled and consensus sequences obtained using the BWA algorithm in UGENE v.33. BWAsuggested: (BWA, RRID:SCR_010910)UGENEsuggested: (Unipro UGENE, RRID:SCR_005579)The resulting TPM data was generated in Geneious and graphs plotted using ggplot 2 (v3.2.0) in R v3.6.1. Geneioussuggested: (Geneious, RRID:SCR_010519)Significance between groups was assessed using a one-way analysis of variance (ANOVA) in PRISM v8.3.1. PRISMsuggested: (PRISM, RRID:SCR_005375)Genome sequence alignment was performed and preliminary maximum likelihood phylogenies of complete genome were reconstructed using RAxML with 1,000 bootstrap replicates in Geneious R9.0.3 software (Biomatters Ltd). RAxMLsuggested: (RAxML, RRID:SCR_006086)To reconstruct a time-scaled phylogeny, an uncorrelated lognormal relaxed-clock model with an exponential growth coalescent prior and the HKY85+Γ substitution model was used in the program BEAST v1.10.4 [20] to simultaneously estimate phylogeny, divergence times and rates of nucleotide substitution. BEASTsuggested: (BEAST, RRID:SCR_010228)The runs were checked for convergence in Tracer v1.7 [21] and that effective sampling size (ESS) values of all parameters was >200. Tracersuggested: (Tracer, RRID:SCR_019121)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
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