Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure

  1. Arghavan Alisoltani
  2. Lukasz Jaroszewski
  3. Mallika Iyer
  4. Arash Iranzadeh
  5. Adam Godzik

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Abstract

Most of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity.

Summary

Monitoring of SARS-CoV-2 genome evolution uncovers increased frequency and non-random distribution of in-frame deletions in recently emerged lineages.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.04.451027: (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
    SentencesResources
    Then, GISAID pipeline used this cleaned data to create MSA file of 961,734 sequences using MAFFT (26) with hCoV-19/Wuhan/WIV04/2019 (EPI_ISL_402124; GenBank: MN996527) used as reference (27).
    GISAID
    suggested: (GISAID, RRID:SCR_018279)
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Visualization of in-frame deletions on proteins’ 3-dimensional (3D) structures: We used PyMol (32), and Coronavirus3D (33) for studying and visualization of IFDs in the context of protein 3-dimensional structure (3D).
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)
    Information on protein domain boundaries was based on PDB (https://www.rcsb.org/) structures when available or on UniProt and the literature (Table S4).
    UniProt
    suggested: (UniProtKB, RRID:SCR_004426)
    Visualization of in-frame deletions on alignment file: We extracted one representative genome for each of the most frequent IFDs (seen in multiple genomes) positioned on protein RDRs from the GISAID MSA file with no gaps in the reference using an in-house Python script and visualized it using R packages ggmsa and Biostrings and counted the number of genomes harboring each type of IFD.
    Python
    suggested: (IPython, RRID:SCR_001658)
    Biostrings
    suggested: (Biostrings, RRID:SCR_016949)
    We used Circos R package to draw the heatmap of recurrence/co-occurrence of top IFDs in PANGO lineage arranges in the order that approximately reflects the evolutionary history of SARS-CoV-2 lineages.
    Circos
    suggested: (Circos, RRID:SCR_011798)

    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: 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.

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  2. Version published to 10.1101/2021.07.04.451027v1 on bioRxiv