Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2

Abstract

SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.

Early mutational signatures and transmissibility of SARS-CoV-2 Gamma and Lambda variants in Chile

“…The COVID-19 pandemic was marked by the high rate at which new SARS-CoV-2 variants emerged 1 , 2 . This high mutational rate could be due to the natural properties of the virus 3 , 4 and the surge in COVID-19 incidence that followed the lifting of major non-pharmaceutical interventions (NPIs) in some countries 5 – 8 . Genomic surveillance (GS) has unveiled the rapid evolution of SARS-CoV-2 and signalled the emergence of variants with increased transmissibility and partial immune escape (e.g., those labelled as Variants of Concern VoC) 9 – 12 , thereby supporting evidence-based decisions in epidemic management 9 , 11 , 13 – 16 .…”