Spatial and Temporal Analysis of SARS-CoV-2 Genome Evolutionary Patterns

Abstract

The spread of SARS-CoV-2 virus accompanied by abundance of sequence data available publicly provides a window for determining the spatio-temporal patterns of viral evolution in response to vaccination. In this study, SARS-CoV-2 genome sequences were collected from seven different countries in the period January 2020 to December 2022. The sequences were classified into three categories, namely: pre-vaccination phase, post-vaccination phase and recent period data. Comparison between the three categories was performed based on parameters like mutation rates, selection pressure (dN/dS ratio) and transition to transversion ratios (Ti/Tv). Similar comparisons were also performed amongst SARS-CoV-2 variants. The comparative analysis showed increase in the percent genomic mutation rates after vaccination and in recent period across different countries from the pre-vaccination phase. The dN/dS ratios showed positive selection that increased after vaccination. The Ti/Tv ratios decreased after vaccination, with C→U and G→U being the most frequent transition and transversion in all the countries. However, U→G was the most frequent transversion in recent period. The Omicron variant had the highest genomic mutation rates while Delta showed the highest dN/dS ratio. Mutation rates were highest in NSP3, S, N and NSP12b before and increased further after vaccination. NSP4 showed the largest change in mutation rates after vaccination. N, ORF8, ORF3a and ORF10 were under highest positive selection before vaccination. They were overtaken by E, S and NSP1 in the after vaccination as well as recent sequences, with the largest change observed in NSP1. Protein-wise dN/dS ratio was also seen to vary across the different variants.