The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages

Abstract

The independent emergence late in 2020 of the B.1.1.7, B.1.351 and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three “501Y lineages” coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favoured convergent mutations at 35 genome sites: mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.

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“…Since its first appearance in November 2019, thousands of SARS-CoV-2 mutations have been identified from across the world (GISAID 2021), including Africa (Inzauale et al 2021; Martin et al 2021;Tao K et al 2021;Wilkinson et al 2021). These have had no major impact on protection induced by vaccines.…”

An entropy-based study on mutational trajectory of SARS-CoV-2 in India

“…Thus, mutations of SARS-CoV-2 need to be studied in order to understand its evolution. In this regard, Martin et al (2021) studied Alpha, Beta and Gamma lineages to understand the evolutionary pattern of the virus. Dorp et al (2020) curated 7666 SARS-CoV-2 genomes to analyse the genomic diversity of SARS-CoV-2, thereby identifying 198 filtered recurrent mutations.…”

A Strategy to Detect Emerging Non-Delta SARS-CoV-2 Variants with a Monoclonal Antibody Specific for the N501 Spike Residue

“…Detection of the N501Y spike mutation with the 2E8 mAb is an efficient way distinguish delta from variants with the N501Y meta-signature [11], such as beta, gamma, mu, C.1.2, and novel N501Y-containing variants yet to emerge. The N501Y mutation has originated independently within multiple viral lineages and is positively selected because it increases infectivity through enhanced ACE2 binding [11,12].…”

“…SARS-CoV-2 variants can be differentiated by amino acid changes in the spike protein receptor-binding domain (RBD) (Table 1), which mediates receptor binding and is one of the major targets of the neutralizing antibody response [4]. One of the most frequent changes is N501Y, which defines a meta-signature of 35 convergent mutations that are associated with increased virulence and evasion of host immunity [11]. The N501 residue lies on the "right shoulder" of the RBD, where it directly contacts the cellular receptor, angiotensin-converting enzyme 2 (ACE2) [12].…”