Emergence of SARS-CoV-2 stains harbouring the signature mutations of both A2a and A3 clade

SARS-CoV-2 strains with both high transmissibility and potential to cause asymptomatic infection is expected to gain selective advantage over other circulating strains having either high transmissibility or ability to trigger asymptomatic infection. The D614G mutation in spike glycoprotein, the characteristic mutation A2a clade, has been associated with high transmissibility, whereas the A3 clade specific mutation L37F in NSP6 protein has been linked with asymptomatic infection. In this study, we performed a comprehensive mutational analysis of 3,77,129 SARS-CoV-2 genomes collected during January, 2020 to December, 2020 from all across the world for the presence of D614G and L37F mutations. Out of 3,77,129 SARS-CoV-2 strains analysed, 14, 598 (3.87%) were found to harbour both the D614G and L37F mutations. Majority of these double mutant SARS-CoV-2 strains were identified in Europe (11097) followed by North America (1915), Asia (980), Oceania (242), Africa (219), and South America (145). Geographical root surveillance revealed their first emergence during February-March in all the six continents. Temporal prevalence analysis from February, 2020 to December, 2020 showed a gradual upsurge in their frequencies worldwide, which strongly demonstrated the adaptive selection of these double mutants. Evolutionary analysis depicted that these double mutants emerged as a new clade in the dendrogram (named as A2a/3), and were sub-divided into four distinct clusters (Cluster I, II, III and IV) according to different sets of coexisting mutations. The frequency distribution pattern showed the global predominance of cluster III (41.42%), followed by cluster IV (23.31%), cluster II (21.02%) and cluster I (14.25%). Overall, our study highlighted the emergence of a unique phylogenetic clade encompassing the double-mutant SARS-CoV-2 strains which may provide a fitness advantage during course of virus evolution.