Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677
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Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.
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SciScore for 10.1101/2021.02.12.21251658: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources PyMol 2.4 (Schödinger PyMolsuggested: (PyMOL, RRID:SCR_000305)Translation alignment of S:Q677 variants was done using Geneious version 2021.0 (Biomatters Limited, Auckland, NZ). Geneioussuggested: (Geneious, RRID:SCR_010519)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Caveats: Selectively …
SciScore for 10.1101/2021.02.12.21251658: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources PyMol 2.4 (Schödinger PyMolsuggested: (PyMOL, RRID:SCR_000305)Translation alignment of S:Q677 variants was done using Geneious version 2021.0 (Biomatters Limited, Auckland, NZ). Geneioussuggested: (Geneious, RRID:SCR_010519)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Caveats: Selectively neutral mutations can become fixed in a lineage purely by chance and human behaviour. For instance, the 20E (EU1) lineage characterized by an S: A222V polymorphism emerged suddenly in Europe over the summer, but thus far has not shown evidence for increased transmissibility (Hodcroft et al., 2020) and instead is thought to have been spread via holiday travel and relaxing summertime restrictions. Additional S variants such as N439K and S477N also rapidly increased in frequency in Europe over the summer and into the fall of 2020. Although S477N reportedly increases affinity for the entry receptor, ACE2 (Zahradník et al., 2021), and both mutations may impact antibody neutralization to some degree (Starr et al., 2020; Weisblum, Schmidt, Zhang, DaSilva, Poston, J. C. Lorenzi, et al., 2020; Liu et al., 2021; Thomson et al., 2021), neither shows any signature of increased transmissibility over the S: D614G background from which they emerged, and neither have become prominent in the United States. Therefore, SARS-CoV-2 variants can emerge and increase greatly in number over time in the absence of any clear or sustained selective advantage. Convergent evolution is a hallmark of positive selection: The repeated evolution of a trait in independent populations provides strong evidence of adaptation. Between August and November, 2020, seven independent lineages of SARS-CoV-2 with S:Q677H or S:Q677P mutations arose and gained in frequency. This coincidental rise and sp...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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