Fig. 5: Fitness values for mutations in the SARS-CoV-2 genome.

A Distribution of fitness values for all defining C → U mutations in SARS-CoV-2 clade 23H compared to all other mutations detected during our short-term evolution experiment (P = 5 × 10⁻⁵, Wilcoxon rank sum test, two-sided alternative). B Details of all defining C → U mutations in SARS-CoV-2 clade 23H. C Although mutations with similar fitness values tend to cluster together, clusters that are positively or negatively selected for tend to be semi-randomly distributed across the genome. Orange bases indicate locations where C → U mutations are selected against, and blue indicates positive selection. The intensity of the color indicates the intensity of selection. D–F However, some regions are strongly enriched in either positive or negative selected cytosines. G–L We plotted the mutations that are most detrimental to viral fitness (ω < 0.5) on the structure of the SARS-CoV-2 spike protein (G–I) and the replisome (J–L) in various orientations. The most interesting mutations are those that occur in clusters, highlighting regions of the viral proteome, or the underlying structure of the genome, that are especially vital to fitness. Three subunits of the spike protein are depicted in pink, blue, and green. Mutations that are predicted to be detrimental are depicted in red (all mutations detected were detrimental) or purple (a subset of mutations detected were detrimental). In J–L, individual units of the replisome are depicted in various colors, including the exonuclease, polymerase, and the viral genome itself.