Natural selection shapes the evolution of SARS-CoV-2 Omicron in Bangladesh.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to give rise to a highly transmissive and immune-escaping variant of concern, known as Omicron. Many aspects of the evolution of SARS-CoV-2 and the driving forces behind the ongoing Omicron outbreaks remain unclear. Substitution at the receptor-binding domain (RBD) in the spike protein is one of the primary strategies of SARS-CoV-2 Omicron to hinder recognition by the host angiotensin-converting enzyme 2 (ACE2) receptor and avoid antibody-dependent defense activation. Here, we scanned for adaptive evolution within the SARS-CoV-2 Omicron genomes reported from Bangladesh in the public database GISAID (www.gisaid.org; dated 2 April 2023). The ratio of the non-synonymous (Ka) to synonymous (Ks) nucleotide substitution rate, denoted as ω, is an indicator of the selection pressure acting on protein-coding genes. A higher proportion of non-synonymous to synonymous substitutions (Ka/Ks or ω > 1) indicates positive selection, while Ka/Ks or ω near zero indicates purifying selection. An equal amount of non-synonymous and synonymous substitutions (Ka/Ks or ω = 1) refers to neutrally evolving sites. We found evidence of adaptive evolution within the spike (S) gene of SARS-CoV-2 Omicron isolated from Bangladesh. In total, 22 codon sites of the S gene displayed a signature of positive selection. The data also highlighted that the receptor-binding motif within the RBD of the spike glycoprotein is a hotspot of adaptive evolution, where many of the codons had ω > 1. Some of these adaptive sites at the RBD of the spike protein are known to be associated with increased viral fitness. The M gene and ORF6 have also experienced positive selection. These results suggest that although purifying selection is the dominant evolutionary force, positive Darwinian selection also plays a vital role in shaping the evolution of SARS-CoV-2 Omicron in Bangladesh.