1.2 Variation in the SARS-CoV2 genome

Mutations in the SARS-CoV2 genome can occur in any of the structural or non-structural genes. For example, the alpha variant (1/Dec/2020) showed 23 mutations from the original strain. 17 of the mutations produced changes in the amino acid sequence of the encoded proteins and 6 did not. Table 8.1 shows the position and type of the 17 ‘non-synonymous’ mutations.

Mutations in the gene sequence are described according to their position and the effect they have on the amino acid sequence. For example the mutation C3267T that occurred at position 3267 in the gene-sequence was a change from a cytosine base (C) to a thymidine (T). This mutation caused a consequent change in the amino acid sequence of the Nsp1-16 protein, T1001I, meaning that at position 1001 of the protein, a threonine residue (T) has been replaced with isoleucine (I). Notice also that there are 3 deletions in the gene encoding the spike protein that have produced deletions (del.) in the protein of 1-3 amino acids.

The key point to take from this table is that the gene encoding the spike protein, which is 10% of the virus genome has more than 50% of the total mutations. In other words, mutation in new variants-of-concern tends to be clustered in the spike protein. Moreover the genome of the variants continued to mutate after it was first identified and sequenced. For example the mutation E484K affecting the spike protein occurred after the initial sequencing of the alpha variant.

Some of the mutations that occurred in one variant appeared in other variants. For example N501Y present in the alpha variant also arose independently in the beta and gamma variants, which implies that this mutation confers some selective advantage in different strains.