Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii). Author summaryIn this study, through analysis of very robust and comprehensive datasets, we identify a plethora of mutations in the SARS-CoV-2 Spike cell surface protein of several variants of concern and multiple variants of interest. We trace an association of such mutations with viral spread in different countries. We further infer the presence of new SARS-CoV-2 sublineages and show that the vast majority of mutations identified in the SARS-CoV-2 Spike protein are under convergent evolution. If we consider every color of a Rubiks cubes face to represent a different mutation of a particular variant, evolutionary convergence can be achieved only when all composite pieces of a single face are of the same color and every face has one unique color. Overall, this raises two important points: we provide insight into the presence of SARS-CoV-2 variants and sub-lineages circulating in very close evolutionary environments and our analyses can serve to facilitate an outlook into the prospective vaccine efficacy against different SARS-CoV-2 strains.
Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution