Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10^-3-10^-4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments.

Keywords: SARS-CoV-2; genetic diversity; molecular adaptation; molecular evolution; rate of evolution; recombination.

Figure 1

Illustration of the SARS-CoV-2 genome structure. Scaled representation of genes along the SARS-CoV-2 genome, including a table with the nucleotide positions between each ORF (Open Reading Frame) and the corresponding encoded proteins according to https://www.ncbi.nlm.nih.gov/nuccore/1798174254 (accessed on 20 November 2022). Structural protein-coding genes are shown in dark blue.

Figure 2

Evolutionary history of main SARS-CoV-2 VOCs. This illustration shows the emergence, establishment, and genetic relationships of the main VOCs according to current knowledge. It also includes a graph describing the predominance of every VOC over time, which we obtained with Nextstrain based on data from GISAID [27,28].