The Red Queen’s Crown: an evolutionary arms race between coronaviruses and mammalian species reflected in positive selection of the ACE2 receptor among many species
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Abstract
The world is going through a global viral pandemic with devastating effects on human life and socioeconomic activities. This pandemic is the result of a zoonotic coronavirus, Severe Acute Respirsatory Syndrom Coronavirus 2 (SARS-CoV-2) which is believed to have originated in bats and transferred to humans possibly through an intermediate host species (Zhou et al. 2020; Coronaviridae Study Group of the International Committee on Taxonomy of Viruses 2020). The virus attacks host cells by attaching to a cell membrane surface protein receptor called ACE2 (Ge et al. 2013; Zhou et al. 2020). Given the critical role of ACE2 as a binding receptor for a number of coronaviruses, we studied the molecular evolution of ACE2 in a diverse range of mammalian species. Using ACE2 as the target protein, we wanted to specifically test the Red Queen hypothesis (Dawkins and Krebs 1979) where the parasite and host engage in an evolutionary arms race which can result in positive selection of their traits associated to their fitness and survival. Our results clearly show a phylogenetically broad evolutionary response, in the form of positive selection detected at the codon-level in ACE2. We see positive selection occurring at deep branches as well as 13 incidents at the species level. We found the strongest level of positive selection in Tasmanian devil ( Sarcophilus harrisii ), donkey ( Equus asinus ), large flying fox ( Pteropus vampyrus ), Weddell seal ( Leptonychotes weddellii ), and dog ( Canis lupus familiaris ). At the codon-level, we found up to 10% of ACE2 codons are impacted by positive selection in the mammalian lineages studied. This phylogenetically broad evolutionary arms race can contribute to the emergence of new strains of coronaviruses in different mammalian lineages with a potential to transfer between species given the common binding receptor ACE2. Our study provides a molecular evolutionary perspective to the current pandemic and sheds light on its evolutionary mechanisms.
“Nothing in biology makes sense except in the light of evolution” (Theodosius Dobzhansky)
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SciScore for 10.1101/2020.05.14.096131: (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 Both analyses were performed using HyPhy 2.5 (Kosakovsky Pond et al. 2020). HyPhysuggested: (HyPhy, RRID:SCR_016162)We corroborated this analysis with known functional domains of the human ACE2 focusing on sites that interact with coronaviruses (see RefSeq NG_012575.1). RefSeqsuggested: (RefSeq, RRID:SCR_003496)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 …SciScore for 10.1101/2020.05.14.096131: (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 Both analyses were performed using HyPhy 2.5 (Kosakovsky Pond et al. 2020). HyPhysuggested: (HyPhy, RRID:SCR_016162)We corroborated this analysis with known functional domains of the human ACE2 focusing on sites that interact with coronaviruses (see RefSeq NG_012575.1). RefSeqsuggested: (RefSeq, RRID:SCR_003496)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.
- No funding statement was detected.
- No protocol registration statement was detected.
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