@article{1ca9698631f5475a8cb9dd8c9a568361,
title = "Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen",
abstract = "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 Coronavirus Disease 2019 (COVID-19) pandemic and to October 2020. Here we assess the types of natural selection taking place in Sarbecoviruses 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 bat Sarbecoviruses. 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 species cannot be discounted, collectively, our results support the progenitor of SARS-CoV-2 being capable of efficient human–human transmission as a consequence of its adaptive evolutionary history in bats, not humans, which created a relatively generalist virus.",
author = "MacLean, {Oscar A.} and Spyros Lytras and Steven Weaver and Singer, {Joshua B.} and Boni, {Maciej F.} and Philippe Lemey and {Kosakovsky Pond}, {Sergei L.} and Robertson, {David L.}",
note = "Funding Information: DLR is funded by the Medical Research Council (MC_UU_1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). SLKP and SW are supported in part by the National Institutes of Health (R01 AI134384 (NIH/NIAID)) and the National Science Foundation (award 2027196). PL acknowledges funding from the European Research Council under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the European Union{\textquoteright}s Horizon 2020 project MOOD (874850), the Wellcome Trust through project 206298/Z/17/Z (The Artic Network) and the Research Foundation – Flanders ({\textquoteleft}Fonds voor Wetenschappelijk Onderzoek – Vlaanderen{\textquoteright}, G066215N, G0D5117N and G0B9317N). MFB is funded by a grant from the Bill and Melinda Gates Foundation (INV-005517) and by NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract (HHS N272201400007C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank all the authors who have kindly deposited and shared genome data. A table with GISAID genome sequence acknowledgments can be found in S6 Table. Credit also needs to be given to the surveillance projects for generating the genome data that are available in GenBank and to the software developers for making the tools we have used freely available. We thank Alex Gunnarsson, Xiaowei Jiang, Joseph Hughes, and Kyriaki Nomikou for thankful comments on the manuscript. Publisher Copyright: {\textcopyright} 2021 MacLean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2021",
month = mar,
day = "12",
doi = "10.1371/journal.pbio.3001115",
language = "English (US)",
volume = "19",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "3",
}