Exceptional diversity and selection pressure on SARS-CoV and SARS-CoV-2 host receptor 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 pathogen transmission between animals and humans highlight the broader need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection. Here, we investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2. We find that the ACE2 gene is under strong selection pressure in bats, the group in which the progenitors of SARS-CoV and SARS-CoV-2 are hypothesized to have evolved, particularly in residues that contact SARS-CoV and SARS-CoV-2. We detect positive selection in non-bat mammals in ACE2 but in a smaller proportion of branches than in bats, without enrichment of selection in residues that contact SARS-CoV or SARS-CoV-2. Additionally, we evaluate similarity between humans and other species in residues that contact SARS-CoV or SARS-CoV-2, revealing potential susceptible species but also highlighting the difficulties of predicting spillover events. This work increases our understanding of the relationship between mammals, particularly bats, and coronaviruses, and provides data that can be used in functional studies of how host proteins are bound by SARS-CoV and SARS-CoV-2 strains.

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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

    NIH rigor criteria are not applicable to paper type.

    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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  2. Version published to 10.1101/2020.04.20.051656 on bioRxiv