Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen

by Oscar A. MacLean, Spyros Lytras, Steven Weaver, Joshua B. Singer, Maciej F. Boni, Philippe Lemey, Sergei L. Kosakovsky Pond, David L. Robertson Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant adaptation to humans since the start of the Coronavi rus Disease 2019 (COVID-19) pandemic and to October 2020. Here we assess the types of natural selection taking place inSarbecoviruses in horseshoe bats versus the early SARS-CoV-2 evolution in humans. While there is moderate evidence of diversifying positive selection in SARS-CoV-2 in humans, it is limited to the early phase of the pandemic, and purifying selection is much weaker in SARS-CoV-2 than in related batSarbecoviruses. In contrast, our analysis detects evidence for significant positive episodic diversifying selection acting at the base of the bat virus lineage SARS-CoV-2 emerged from, accompanied by an adaptive depletion in CpG composition presumed to be linked to the action of antiviral mechanisms in these ancestral bat hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor about 1976), is a recombinant with a structure that includes differential CpG content in Spike; clear evidence of coinfection and evolution in bats without involvement of other species. While an undiscovered “facilitating” intermediate s...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research