Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

Abstract

Despite the appearance of variant SARS-CoV-2 viruses with altered receptor-binding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively-evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein-coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit.

Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

“…Regression analysis (root-to-tip distance) based on complete genomes of pan India isolates (Dataset_3; Supplementary File S4) depicted temporal signals. Similar observations have been reported earlier [51,52]. The NSR estimated using complete genomes of Indian isolates (6.73 × 10 −2 subs/site/year; 95% HPD: 5 × 10 −3 to 7 × 10 −2 ) is higher as compared to that reported for Southeast Asia data (1.44 × 10 −3 subs/site/year; 95% HPD 1.292 × 10 −3 to 1.613 × 10 −3 ) and global (representative) VoC isolates (6.5 × 10 −4 subs/site/year; 95% HPD 0.58 − 0.77 × 10 −3 ) [51][52][53].…”

“…Similar observations have been reported earlier [51,52]. The NSR estimated using complete genomes of Indian isolates (6.73 × 10 −2 subs/site/year; 95% HPD: 5 × 10 −3 to 7 × 10 −2 ) is higher as compared to that reported for Southeast Asia data (1.44 × 10 −3 subs/site/year; 95% HPD 1.292 × 10 −3 to 1.613 × 10 −3 ) and global (representative) VoC isolates (6.5 × 10 −4 subs/site/year; 95% HPD 0.58 − 0.77 × 10 −3 ) [51][52][53]. The estimated NSR in Indian data is higher than the NSR of known RNA viruses and similar to that reported for viroids [54].…”

The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia

“…It was also shown to bind to CD14+ monocytes, which reduces their antigen representation capacity and triggers the production of proinflammatory cytokines [ 40 ]. Nonsynonymous mutations in ORF7a contribute to SARS-CoV-2 clade success [ 18 ]. C-terminal truncations of ORF7a are frequent and were shown to affect viral replication [ 41 ].…”

“…While Delta clearly has increased fitness compared to ancestral strains, whether its sublineages change its properties further is less clear [15][16][17]. Still, adaptive evolution of SARS-CoV-2 in the human genome continues [18], highlighting the need for surveillance of novel variants.…”

SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

“…Its rapid rise to dominance has been attributed to greater levels of transmissibility [4,5] than previously circulating variants with the reproduction number estimated to be over two-fold higher [6], as well as possible reduced vaccine effectiveness against infection [3]. Since its global dissemination, continued adaptive evolution has led to a diverse set of Delta sub-lineages, with distinct combinations of mutations (especially on the spike protein) [7,8].…”