SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants

Abstract

Since its emergence as a pneumonia-like outbreak in the Chinese city of Wuhan in late 2019, the novel coronavirus disease COVID-19 has spread widely to become a global pandemic. The first case of COVID-19 in India was reported on 30 January 2020 and since then it has affected more than ten million people and resulted in around 150,000 deaths in the country. Over time, the viral genome has accumulated mutations as it passes through its human hosts, a common evolutionary mechanism found in all microorganisms. This has implications for disease surveillance and management, vaccines and therapeutics, and the emergence of reinfections. Sequencing the viral genome can help monitor these changes and provides an extraordinary opportunity to understand the genetic epidemiology and evolution of the virus as well as tracking its spread in a population. Here we review the past year in the context of the phylogenetic analysis of variants isolated over the course of the pandemic in India and highlight the importance of continued sequencing-based surveillance in the country.

Figure 1

The SARS-CoV-2 genome is ~30Kb and consists of genes encoding structural and non-structural proteins. The structural proteins are nucleocapsid (N), spike (S), membrane (M), and envelope (E) proteins. Each box indicates a gene. The numbers on the axis indicate genome coordinates.

Figure 2

A simplified phylogenetic tree showing the divergence of clades from the ancestral root (Wuhan) and their corresponding clade-defining mutations. The boxes indicate clades. Boxes of the same color indicate derived clades sharing the same mutations as the parent. The clade nomenclature (19 and 20) as specified by Nextstrain is given within the box, while the GISAID clade is mentioned in parentheses. The text on the right shows the clade defining mutations of the respective clade and is in the order of protein, amino acid and position followed by the amino acid change. The month above the branches indicates the inferred month of emergence of specific clades. Currently, 20A, 20B and 20C are the globally dominant clades.

Figure 3

Timeline of clade distribution in India (top) and across different states (state abbreviations are indicated on the left). Clades are differentiated by colors as per the legend on the top while size of the bubble indicates their prevalence. As seen in the country track on the top, A3i clade (green) was prevalent during the months of March-May and was eventually overtaken by the A2a clade (blue).

Figure 4

Plot showing the number of mutations identified across genes in the SARS-CoV-2 genome, from Indian samples. ORF1a, ORF1b and S show higher frequency of mutations compared to the rest of the genes.

Figure 5

Representation of the spike gene indicating key mutations that are a cause for concern and require monitoring in India. The various sub-domains of the spike gene are shown as colored boxes and defined in the legend. The position and color of each line indicates the location of the particular mutation, defined above the gene.