The Novel Coronavirus Enigma: Phylogeny and Analyses of Coevolving Mutations Among the SARS-CoV-2 Viruses Circulating in India.

Background: The RNA genome of the emerging novel coronavirus is rapidly mutating, and its human-to-human transmission rate is increasing. Hence, temporal dissection of their evolutionary dynamics, the nature of variations among different strains, and understanding the single nucleotide polymorphisms in the endemic settings are crucial. Delineating the heterogeneous genomic constellations of this novel virus will help us understand its complex behavior in a particular geographical region.

Objective: This is a comprehensive analysis of 95 Indian SARS-CoV-2 genome sequences available from the Global Initiative on Sharing All Influenza Data (GISAID) repository during the first 6 months of 2020 (January through June). Evolutionary dynamics, gene-specific phylogeny, and the emergence of the novel coevolving mutations in 9 structural and nonstructural genes among circulating SARS-CoV-2 strains across 12 different Indian states were analyzed.

Methods: A total of 95 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID database. Molecular Evolutionary Genetics Analysis, version X software was used to construct the 9 phylogenetic dendrograms based on nucleotide sequences of the SARS-CoV-2 genes. Analyses of the coevolving mutations were done in comparison to the prototype SARS-CoV-2 from Wuhan, China. The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation.

Results: Phylogenetic analyses revealed the evolution of "genome-type clusters" and adaptive selection of "L"-type SARS-CoV-2 strains with genetic closeness to the bat severe acute respiratory syndrome-like coronaviruses. These strains were distant to pangolin or Middle East respiratory syndrome-related coronavirus strains. With regard to the novel coevolving mutations, 2 groups have been seen circulating in India at present, the "major group" (66/95, 69.4%) and the "minor group" (21/95, 22.1%) , harboring 4 and 5 coexisting mutations, respectively. The "major group" mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6 gene), were unique to the Indian isolates.

Conclusions: This study highlights the rapidly evolving SARS-CoV-2 virus and the cocirculation of multiple clades and subclades. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, interpreting changes in viral pathogenesis, and designing vaccines or other therapeutics.