Genomic landscape of alpha-variant of SARS-CoV-2 circulated in Pakistan

Abstract

In this study, we investigated the genomic variability of alpha-VOC of SARS-CoV-2 in Pakistan, in context of the global population of this variant. A set of 461 whole-genome sequences of Pakistani samples of alpha-variant, retrieved from GISAID, were aligned in MAFFT and used as an input to the Coronapp web-application. Phylogenetic tree was constructed through maximum-likelihood method by downloading the 100 whole-genome sequences of alpha-variant for each of the 12 countries having the largest number of Pakistani diasporas. We detected 1725 mutations, which were further categorized into 899 missense mutations, 654 silent mutations, 52 mutations in non-coding regions, 25 in-frame deletions, 01 in-frame insertion, 51 frameshift deletions, 21 frameshift insertions, 21 stop-gained variants, and 1 stop-gained deletion. We found NSP3 and Spike as the most variable proteins with 355 and 233 mutations respectively. However, some characteristic mutations like Δ144(S), G204R(N), and T1001I, I2230T, del3675–3677(ORF1ab) were missing in the Pakistani population of alpha-variant. Likewise, R1518K(NSP3), P83L(NSP9), and A52V, H164Y(NSP13) were found for the first time in this study. Interestingly, Y145 deletion(S) had 99% prevalence in Pakistan but globally it was just 4.2% prevalent. Likewise, R68S substitution (ORF3a), F120 frameshift deletion, L120 insertion, L118V substitution (ORF8), and N280Y(NSP2) had 20.4%, 14.3%, 14.8%, 9.1%, 13.9% prevalence locally but globally they were just 0.1%, 0.2%, 0.04%, 1.5%, and 2.4% prevalent respectively. The phylogeny analysis revealed that majority of Pakistani samples were grouped together in the same clusters with Italian, and Spanish samples suggesting the transmission of alpha-variant to Pakistan from these western European countries.