The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins
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Abstract
The unprecedented pace of the sequencing of the SARS-CoV-2 virus genomes provides us with unique information about the genetic changes in a single pathogen during ongoing pandemic. By the analysis of close to 200,000 genomes we show that the patterns of the SARS-CoV-2 virus mutations along its genome are closely correlated with the structural and functional features of the encoded proteins. Requirements of foldability of proteins’ 3D structures and the conservation of their key functional regions, such as protein-protein interaction interfaces, are the dominant factors driving evolutionary selection in protein-coding genes. At the same time, avoidance of the host immunity leads to the abundance of mutations in other regions, resulting in high variability of the missense mutation rate along the genome. “Unexplained” peaks and valleys in the mutation rate provide hints on function for yet uncharacterized genomic regions and specific protein structural and functional features they code for. Some of these observations have immediate practical implications for the selection of target regions for PCR-based COVID-19 tests and for evaluating the risk of mutations in epitopes targeted by specific antibodies and vaccine design strategies.
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SciScore for 10.1101/2020.08.10.244756: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Alignment, variant calling, and annotation: We calculated a multiple sequence alignment (MSA) of all high-quality SARS-CoV-2 genomes using MAFFT version 7 (https://mafft.cbrc.jp/alignment/server/) with the default parameters. MAFFTsuggested: (MAFFT, RRID:SCR_011811)The MSA file was then processed using SNP-sites[33] and BCFtools version 1.9[34] for variant calling and variant normalizations, respectively. BCFtoolssuggested: (SAMtools/BCFtools, RRID:SCR_005227)To annotate variants, we used SnpEff (http://snpeff.sourceforge.net/). SnpEffsuggested: (SnpEff, RRID:SCR_005191)The collected … SciScore for 10.1101/2020.08.10.244756: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Alignment, variant calling, and annotation: We calculated a multiple sequence alignment (MSA) of all high-quality SARS-CoV-2 genomes using MAFFT version 7 (https://mafft.cbrc.jp/alignment/server/) with the default parameters. MAFFTsuggested: (MAFFT, RRID:SCR_011811)The MSA file was then processed using SNP-sites[33] and BCFtools version 1.9[34] for variant calling and variant normalizations, respectively. BCFtoolssuggested: (SAMtools/BCFtools, RRID:SCR_005227)To annotate variants, we used SnpEff (http://snpeff.sourceforge.net/). SnpEffsuggested: (SnpEff, RRID:SCR_005191)The collected experimental and modeled biological assemblies of SARS-CoV-2 proteins were used to calculate solvent exposure with the GetArea program[37]. GetAreasuggested: NoneResults 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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.08.10.244756: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Antibody binding and ACE2 areas were derived from separate PDB entries (Ids of PDB entries used to define epitopes and RBD-ACE2 interface are shown above the 3D insets). ACE2suggested: NoneSoftware and Algorithms Sentences Resources Alignment, variant calling, and annotation We calculated a multiple sequence alignment (MSA) of all high-quality SARS-CoV-2 genomes using MAFFT version 7 (https://mafft.cbrc.jp/alignment/server/) with the default parameters. …SciScore for 10.1101/2020.08.10.244756: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Antibody binding and ACE2 areas were derived from separate PDB entries (Ids of PDB entries used to define epitopes and RBD-ACE2 interface are shown above the 3D insets). ACE2suggested: NoneSoftware and Algorithms Sentences Resources Alignment, variant calling, and annotation We calculated a multiple sequence alignment (MSA) of all high-quality SARS-CoV-2 genomes using MAFFT version 7 (https://mafft.cbrc.jp/alignment/server/) with the default parameters. MAFFTsuggested: (MAFFT, RRID:SCR_011811)The MSA file was then processed using SNP-sites[33] and BCFtools version 1.9[34] for variant calling and variant normalizations, respectively. BCFtoolssuggested: (SAMtools/BCFtools, RRID:SCR_005227)The collected experimental and modeled biological assemblies of SARS-CoV-2 proteins were used to calculate solvent exposure with the GetArea program[37]. GetAreasuggested: NoneResults 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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
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.
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