No evidence for distinct types in the evolution of SARS-CoV-2

Abstract

A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more 'aggressive' than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.

Keywords: COVID-19; SARS-CoV-2; adaptation.

Figure 1.

A visualization of the genetic variation observed in the SARS-CoV-2 pandemic sequences up until the 12 March 2020. Nonsynonymous (pink) and synonymous (green) substitutions (with respect to Wuhan-Hu-1, GenBank accession number MN908947) are represented in colour in each row, with rows labelled with the genome position and corresponding ORF on the side. The mutations are plotted in a grid format where each column is a sample and each row is a unique mutation at a given genome position; mutations have been filtered to only display those observed in more than one sample (seventy-four nonsynonymous and forty-one synonymous). The genome positions of some of the most common mutations have been labelled directly on the plot. The plot was created using the d3heatmap package in R, and the sample columns are clustered using Ward’s method.

Figure 2.

A phylogenetic tree of the SARS-CoV-2 outbreak data as of 2 March 2020. The tree was generated by the CoV-GLUE resource which uses the RAXML software (Stamatakis 2014). Branches and tips coloured blue have a serine at Codon 84 in ORF8, red tips and branches have a leucine.

Figure 3.

Schematic phylogenetic trees, not drawn to scale, inferred from nonsynonymous (left) and synonymous sites (right) using the estimated divergence values per site from Table 1 of Tang et al. (2020), assuming clock-like mutation rates. The last common ancestor (LCA) of the SARS-CoV-2 outbreak is much closer to that of the LCA shared with the bat-infecting RaTG13 sample in nonsynonymous sites than in synonymous sites. Accession numbers from GISAID for the RaTG13 and Guandong (GD) Pangolin-CoV samples are EPI_ISL_402131 and EPI_ISL_410721, respectively.