The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus.

BioRxiv : the Preprint Server for Biology
H. L. WellsS J Anthony

Abstract

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. Here, we report three sequences of a novel sarbecovirus 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. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. 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 lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hy...Continue Reading

Citations

Jan 31, 2021·Human Genomics·Sally Badawi, Bassam R Ali

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Datasets Mentioned

BETA
MT732776
MW183243

Methods Mentioned

BETA
X-ray
PCR
GISAID

Software Mentioned

BEAST2
hACE2
Bowtie2
GISAID
Beagle
FigTree
3SEQ
Tracer
BEAST
Muscle

Related Concepts

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