Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

  1. Hannah K. Frank
  2. David Enard
  3. Scott D. Boyd

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Abstract

Pandemics originating from non-human animals highlight the need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection and/or potential reservoirs to mitigate public health and conservation concerns. Multiple zoonotic coronaviruses, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV), SARS-CoV-2 and Middle Eastern respiratory syndrome-associated coronavirus (MERS-CoV), are hypothesized to have evolved in bats. We investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2, and dipeptidyl-peptidase 4 (DPP4 or CD26), the host protein bound by MERS-CoV, in the largest bat datasets to date. Both the ACE2 and DPP4 genes are under strong selection pressure in bats, more so than in other mammals, and in residues that contact viruses. Additionally, mammalian groups vary in their similarity to humans in residues that contact SARS-CoV, SARS-CoV-2 and MERS-CoV, and increased similarity to humans in binding residues is broadly predictive of susceptibility to SARS-CoV-2. This work augments our understanding of the relationship between coronaviruses and mammals, particularly bats, provides taxonomically diverse data for studies of how host proteins are bound by coronaviruses and can inform surveillance, conservation and public health efforts.

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  1. Version published to 10.1098/rspb.2022.0193
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    SciScore for 10.1101/2020.04.20.051656: (What is this?)

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

    Table 1: Rigor

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    From these species, we isolated DNA from tissue using the Qiagen DNeasy Blood and Tissue kit (Valencia, CA, USA) and created genomic libraries using the NEBNext Ultra II kit (New England BioLabs; Ipswich, MA, USA), according to manufacturer’s instructions.
    New England BioLabs
    suggested: (New England Biolabs, SCR_013517)
    We compared amino acid sequences across 24 positions known to be important for binding of SARS-CoV and/or SARS-CoV-2 as determined by others6,8,10,11,14–16.
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)
    Additionally, to determine whether bats, and specifically the family Rhinolophidae, are under strong selection to adapt to viruses we used the adaptive branch-site random effects model test of positive selection, aBSREL21, as implemented in HyPhy, version 2.5.841, using a pruned subset of five phylogenetic hypotheses chosen from the pseudo-posterior distribution of Upham et al.17 to account for phylogenetic uncertainty.
    HyPhy
    suggested: (HyPhy, SCR_016162)

    Results from OddPub: Thank you for sharing your data.

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  3. Version published to 10.1101/2020.04.20.051656v1 on bioRxiv