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

ABSTRACT: Given the importance of variant SARS-CoV-2 viruses with altered receptor-binding or antigenic phenotypes, we sought to quantify the degree to which adaptive evolution is driving accumulation of mutations in the SARS-CoV-2 genome. Here we assessed adaptive evolution across genes in the SARS-CoV-2 genome by correlating clade growth with mutation accumulation as well as by comparing rates of nonsynonymous to synonymous divergence, clustering of mutations across the SARS-CoV-2 phylogeny and degree of convergent evolution of individual mutations. We find that spike S1 is the focus of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Adaptive changes in S1 accumulated rapidly, resulting in a remarkably high ratio of nonsynonymous to synonymous divergence that is 2.5X greater than that observed in HA1 at the beginning of the 2009 H1N1 pandemic.

SUBMITTER: Kistler KE

PROVIDER: S-EPMC8452090 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Kistler Kathryn E KE Huddleston John J Bedford Trevor T

bioRxiv : the preprint server for biology 20220119

Given the importance of variant SARS-CoV-2 viruses with altered receptor-binding or antigenic phenotypes, we sought to quantify the degree to which adaptive evolution is driving accumulation of mutations in the SARS-CoV-2 genome. Here we assessed adaptive evolution across genes in the SARS-CoV-2 genome by correlating clade growth with mutation accumulation as well as by comparing rates of nonsynonymous to synonymous divergence, clustering of mutations across the SARS-CoV-2 phylogeny and degree o ...[more]

PMID: 34545361

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Project description:The clue behind the SARS-CoV-2 origin is still a matter of debate. Here, we report that SARS-CoV-2 has gained a novel spike protein S1-N-terminal domain (S1-NTD). In our CLuster ANalysis of Sequences (CLANS) analysis, SARS-CoV/SARS-CoV-2 S1-NTDs displayed a close relationship with OC43 and HKU1. However, in the complete and S1-NTD-free spike protein, SARS-CoV/SARS-CoV-2 revealed closeness with MERS-CoV. Further, we have divided the S1-NTD of SARS-CoV-2 related viruses into three distinct types (Type-I to III S1-NTD) and the S1-NTD of viruses associated with SARS-CoVs into another three classes (Type-A to C S1-NTD) using CLANS and phylogenetic analyses. In particular, the results of our study indicate that SARS-CoV-2, RaTG13, and BANAL-20-52 viruses carry Type-I-S1-NTD and other SARS-CoV-2-related-bat viruses have Type-II and III. In addition, it was revealed that the Pangolin-GX and Pangolin-Guangdong lineages inherited Type-I-like and Type-II-like S1-NTD, respectively. Then our CLANS study shows the potential for evolution of Type-I and Type-III S1-NTD from SARS-CoV-related viruses Type-A and Type-B S1-NTDs, respectively. Furthermore, our analysis clarifies the possibility that Type-II S1-NTDs may have evolved from Type-A-S1-NTD of SARS-CoV-related viruses through Type-I S1-NTDs. We also observed that BANAL-20-103, BANAL-20-236, and Pangolin-Guangdong-lineage viruses containing Type-II-like S1-NTD are very close to SARS-CoV-2 in spike genetic areas other than S1-NTD. Possibly, it suggests that the common ancestor spike gene of SARS-CoV-2/RaTG13/BANAL-20-52-like virus may have evolved by recombining the Pangolin-Guangdong/BANAL-20-103/BANAL-20-236-like spike gene to Pangolin-GX-like Type-I-like-S1-NTD in the unsampled bat or undiscovered intermediate host or possibly pangolin. These may then have evolved into SARS-CoV-2, RaTG13, and BANAL-20-52 virus spike genes by host jump mediated evolution. The potential function of the novel Type-I-S1-NTD and other types of S1-NTDs needs to be studied further to understand better its importance in the ongoing COVID-19 outbreak and for future pandemic preparedness.

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Dataset Information

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

Publications

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

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