Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms

  1. Francisco Barona-Gómez
  2. Luis Delaye
  3. Erik Díaz-Valenzuela
  4. Fabien Plisson
  5. Arely Cruz-Pérez
  6. Mauricio Díaz-Sánchez
  7. Christian A. García-Sepúlveda
  8. Alejandro Sanchez-Flores
  9. Rafael Pérez-Abreu
  10. Francisco J. Valencia-Valdespino
  11. Natali Vega-Magaña
  12. José Francisco Muñoz-Valle
  13. Octavio Patricio García-González
  14. Sofía Bernal-Silva
  15. Andreu Comas-García
  16. Angélica Cibrián-Jaramillo

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Abstract

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1–S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

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  1. Version published to 10.1099/mgen.0.000684 on Access Microbiology
  2. Version published to 10.1101/2021.05.18.21256128v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.18.21256128: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethical committee clearance: Ethical committee clearance.
    Consent: An informed written consent for the use of surveillance samples was obtained from all patients.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Detection of San Luis Potosí SARS-CoV2 positive samples was done with the GeneFinder COVID-19 PLUS RealAmp Kit.
    GeneFinder
    suggested: (GENEFINDER, RRID:SCR_009190)
    We identified 337 combinations of mutations and 315 unique mutations from 1552 (two sequences were filtered out because of quality issues) sequences using in-house Perl and Python scripts.
    Python
    suggested: (IPython, RRID:SCR_001658)
    We transformed the output file to study the incidence for 315 mutations, we grouped them in 11 clades, and we studied their covariances between one another, applying in-house scripts with R packages: tidyverse (Wickham et al. 2019), circlize (Gu et al. 2014), and Python modules: NumPy (Harris et al. 2020), Pandas (McKinney et al. 2010), matplotlib (Hunter, 2007), seaborn (Waskom et al. 2017)
    NumPy
    suggested: (NumPy, RRID:SCR_008633)
    matplotlib
    suggested: (MatPlotLib, RRID:SCR_008624)
    They were then mapped to the NC_045512.2 version of the SARS-CoV-2 reference genome using BWA (Li & Durbin 2009) with default parameters.
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Sam alignments were then converted to bam files and sorted using samtools (Li et al. 2009).
    samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    (Schrodinger LLC, http://www.pymol.org).
    http://www.pymol.org
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: Thank you for sharing your code and data.

    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 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.
    • 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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2021.05.18.21256128v1 on medRxiv