An Evolutionary Insight Into the Heterogeneous Severity Pattern of the SARS-CoV-2 Infection

Abstract

The ongoing pandemic of COVID-19 has elaborated an idiosyncratic pattern of SARS-CoV-2-induced symptoms in the human host. Some populations have succumbed to the SARS-CoV-2 infection in large numbers during this pandemic, whereas others have shown a resilient side by manifesting only milder or no symptoms at all. This observation has relayed the onus of the heterogeneous pattern of SARS-CoV-2-induced critical illness among different populations to the host genetic factors. Here, the evolutionary route was explored and three genetic loci, i.e., rs10735079, rs2109069, and rs2236757, associated with COVID-19 were analyzed. Among the three, the risk allele A at genetic locus rs2236757 residing in the IFNAR2 gene was observed to have undergone recent positive selection in the African population.

Keywords: COVID-19; SNP variants; host genetic factors; natural selection; population genomics.

FIGURE 1

EHH plots and Bifurcation Diagrams for SNP rs2236757 (in non-African Populations). EHH plots and Bifurcation Diagrams for SNP rs2236757 in Asian (A), American (B) and European (C) populations. EHH = l on Y-axis indicates all haplotypes carrying either ancestral or derived state of the allele are matching upto this point. X-axis contains coordinates for human chromosome 21. Ancestral allele is shown before the derived allele, separated by a “>” symbol. In the EHH plots, smaller area under the curve for both ancestral and derived alleles (G > A) shows no signs of recent positive selection in any of the aforementioned populations.

FIGURE 2

EHH plot and Bifurcation Diagrams for SNP rs2236757 (in African Populations). EHH plots and Bifurcation Diagrams of SNP rs2236757in African populations. (A) Bifurcation Diagram of the derived variant of the SNP rs2236757 (shown in blue) shows long haplotype and absolutely no branching at the nodes upto 14.6 kb region. (B) EHH plot for SNP rs2236757 shows derived allele A (shown in blue) is under positive selection. EHH = 1 indicates all haplotypes carrying either ancestral or derived state of the allele are matching upto this point.