The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus
Vincent J. Munster,
Posted 07 Jul 2020
bioRxiv DOI: 10.1101/2020.07.07.190546
Posted 07 Jul 2020
SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Further, we report three novel sarbecoviruses from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Here, we show that recombination is most likely responsible for the observed patterns of ACE2 usage among sarbecoviruses. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the progenitor of SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious, show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and propose a competitive release hypothesis to explain how this recombination event could have been evolutionarily advantageous. The findings from this study provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where ACE2-using viruses have been found to date, as well as other regions including Africa, where these viruses have only recently been discovered. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 558 times
- Download rankings, all-time:
- Site-wide: 29,067 out of 94,912
- In evolutionary biology: 1,899 out of 5,736
- Year to date:
- Site-wide: 4,607 out of 94,912
- Since beginning of last month:
- Site-wide: 522 out of 94,912
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!