The Emergence of SARS-CoV-2 Variants of Concern Is Driven by Acceleration of the Substitution Rate
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Abstract
The ongoing SARS-CoV-2 pandemic has seen an unprecedented amount of rapidly generated genome data. These data have revealed the emergence of lineages with mutations associated to transmissibility and antigenicity, known as variants of concern (VOCs). A striking aspect of VOCs is that many of them involve an unusually large number of defining mutations. Current phylogenetic estimates of the substitution rate of SARS-CoV-2 suggest that its genome accrues around two mutations per month. However, VOCs can have 15 or more defining mutations and it is hypothesized that they emerged over the course of a few months, implying that they must have evolved faster for a period of time. We analyzed genome sequence data from the GISAID database to assess whether the emergence of VOCs can be attributed to changes in the substitution rate of the virus and whether this pattern can be detected at a phylogenetic level using genome data. We fit a range of molecular clock models and assessed their statistical performance. Our analyses indicate that the emergence of VOCs is driven by an episodic increase in the substitution rate of around 4-fold the background phylogenetic rate estimate that may have lasted several weeks or months. These results underscore the importance of monitoring the molecular evolution of the virus as a means of understanding the circumstances under which VOCs may emerge.
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SciScore for 10.1101/2021.08.29.21262799: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources We downloaded 20 randomly selected sequences from the four VOCs to generate a data set of 180 genomes, which we aligned using MAFFT (Katoh and Standley, 2013). MAFFTsuggested: (MAFFT, RRID:SCR_011811)We ensured that all VOC samples that were monophyletic with other VOC samples with an approximate Bayes support <0.95. 4.2 Bayesian phylogenetic analyses: Our Bayesian analyses require specifying a substitution model, a tree, prior, priors for all parameters in BEAST 1.10 (Suchard et al., 2018). BEASTsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: We did not detect open data. We also …
SciScore for 10.1101/2021.08.29.21262799: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources We downloaded 20 randomly selected sequences from the four VOCs to generate a data set of 180 genomes, which we aligned using MAFFT (Katoh and Standley, 2013). MAFFTsuggested: (MAFFT, RRID:SCR_011811)We ensured that all VOC samples that were monophyletic with other VOC samples with an approximate Bayes support <0.95. 4.2 Bayesian phylogenetic analyses: Our Bayesian analyses require specifying a substitution model, a tree, prior, priors for all parameters in BEAST 1.10 (Suchard et al., 2018). BEASTsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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