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Title: Emergence of SARS-CoV-2 through recombination and strong purifying selection

Abstract

COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species, together with frequent recombination among coronaviruses, suggests a common evolutionary mechanism that could lead to new emerging human coronaviruses.

Authors:
ORCiD logo [1];  [2]; ORCiD logo [1];  [2]; ORCiD logo [3];  [4];  [1]; ORCiD logo [2]; ORCiD logo [5]; ORCiD logo [6]
  1. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
  2. Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
  3. Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, TX 79968, USA.
  4. Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University, New York, NY 10016, USA.
  5. Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA., New Mexico Consortium, Los Alamos, NM 87545, USA.
  6. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA., National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1635592
Alternate Identifier(s):
OSTI ID: 1726193
Report Number(s):
LA-UR-20-22544
Journal ID: ISSN 2375-2548; eabb9153
Grant/Contract Number:  
89233218CNA000001; 20200554ECR
Resource Type:
Published Article
Journal Name:
Science Advances
Additional Journal Information:
Journal Name: Science Advances Journal Volume: 6 Journal Issue: 27; Journal ID: ISSN 2375-2548
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Li, Xiaojun, Giorgi, Elena E., Marichannegowda, Manukumar Honnayakanahalli, Foley, Brian, Xiao, Chuan, Kong, Xiang-Peng, Chen, Yue, Gnanakaran, S., Korber, Bette, and Gao, Feng. Emergence of SARS-CoV-2 through recombination and strong purifying selection. United States: N. p., 2020. Web. doi:10.1126/sciadv.abb9153.
Li, Xiaojun, Giorgi, Elena E., Marichannegowda, Manukumar Honnayakanahalli, Foley, Brian, Xiao, Chuan, Kong, Xiang-Peng, Chen, Yue, Gnanakaran, S., Korber, Bette, & Gao, Feng. Emergence of SARS-CoV-2 through recombination and strong purifying selection. United States. https://doi.org/10.1126/sciadv.abb9153
Li, Xiaojun, Giorgi, Elena E., Marichannegowda, Manukumar Honnayakanahalli, Foley, Brian, Xiao, Chuan, Kong, Xiang-Peng, Chen, Yue, Gnanakaran, S., Korber, Bette, and Gao, Feng. Fri . "Emergence of SARS-CoV-2 through recombination and strong purifying selection". United States. https://doi.org/10.1126/sciadv.abb9153.
@article{osti_1635592,
title = {Emergence of SARS-CoV-2 through recombination and strong purifying selection},
author = {Li, Xiaojun and Giorgi, Elena E. and Marichannegowda, Manukumar Honnayakanahalli and Foley, Brian and Xiao, Chuan and Kong, Xiang-Peng and Chen, Yue and Gnanakaran, S. and Korber, Bette and Gao, Feng},
abstractNote = {COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species, together with frequent recombination among coronaviruses, suggests a common evolutionary mechanism that could lead to new emerging human coronaviruses.},
doi = {10.1126/sciadv.abb9153},
journal = {Science Advances},
number = 27,
volume = 6,
place = {United States},
year = {2020},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1126/sciadv.abb9153

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Works referenced in this record:

Distinct viral clades of SARS‐CoV‐2: Implications for modeling of viral spread
journal, June 2020


Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding
journal, February 2020


GISAID: Global initiative on sharing all influenza data – from vision to reality
journal, March 2017


Origin and evolution of pathogenic coronaviruses
journal, December 2018


Structural basis of receptor recognition by SARS-CoV-2
journal, March 2020


Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor
journal, October 2013

  • Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou
  • Nature, Vol. 503, Issue 7477
  • DOI: 10.1038/nature12711

Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses
journal, February 2020


Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan
journal, January 2020


Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus
journal, November 2017


HIV-1 did not contribute to the 2019-nCoV genome
journal, January 2020


Clustal W and Clustal X version 2.0
journal, September 2007


Protein Structure and Function Prediction Using I‐TASSER
journal, December 2015


Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission
journal, November 2009

  • Graham, Rachel L.; Baric, Ralph S.
  • Journal of Virology, Vol. 84, Issue 7
  • DOI: 10.1128/JVI.01394-09

ICM?A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation
journal, May 1994

  • Abagyan, Ruben; Totrov, Maxim; Kuznetsov, Dmitry
  • Journal of Computational Chemistry, Vol. 15, Issue 5
  • DOI: 10.1002/jcc.540150503

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
journal, March 2020


A Computer Program Designed to Screen Rapidly for HIV Type 1 Intersubtype Recombinant Sequences
journal, November 1995

  • Siepel, Adam C.; Halpern, Aaron L.; Macken, Catherine
  • AIDS Research and Human Retroviruses, Vol. 11, Issue 11
  • DOI: 10.1089/aid.1995.11.1413

Data, disease and diplomacy: GISAID's innovative contribution to global health: Data, Disease and Diplomacy
journal, January 2017

  • Elbe, Stefan; Buckland-Merrett, Gemma
  • Global Challenges, Vol. 1, Issue 1
  • DOI: 10.1002/gch2.1018

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination
journal, January 1999


Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
journal, April 2020


The proximal origin of SARS-CoV-2
journal, March 2020


A new coronavirus associated with human respiratory disease in China
journal, February 2020


SARS-like WIV1-CoV poised for human emergence
journal, March 2016

  • Menachery, Vineet D.; Yount, Boyd L.; Sims, Amy C.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 11
  • DOI: 10.1073/pnas.1517719113

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
journal, November 2003

  • Li, Wenhui; Moore, Michael J.; Vasilieva, Natalya
  • Nature, Vol. 426, Issue 6965
  • DOI: 10.1038/nature02145

Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins
journal, March 2020


Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
journal, February 2020

  • Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.
  • Science, Vol. 367, Issue 6483
  • DOI: 10.1126/science.abb2507

Evidence for Camel-to-Human Transmission of MERS Coronavirus
journal, June 2014

  • Azhar, Esam I.; El-Kafrawy, Sherif A.; Farraj, Suha A.
  • New England Journal of Medicine, Vol. 370, Issue 26
  • DOI: 10.1056/NEJMoa1401505

Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2
journal, March 2020


Structure, Function, and Evolution of Coronavirus Spike Proteins
journal, September 2016


Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica)
journal, October 2019

  • Liu, Ping; Chen, Wu; Chen, Jin-Ping
  • Viruses, Vol. 11, Issue 11
  • DOI: 10.3390/v11110979

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence
journal, November 2015

  • Menachery, Vineet D.; Yount, Boyd L.; Debbink, Kari
  • Nature Medicine, Vol. 21, Issue 12
  • DOI: 10.1038/nm.3985

Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China
journal, February 2018


A Simple, Fast, and Accurate Algorithm to Estimate Large Phylogenies by Maximum Likelihood
journal, October 2003


Bats and Coronaviruses
journal, January 2019

  • Banerjee, Arinjay; Kulcsar, Kirsten; Misra, Vikram
  • Viruses, Vol. 11, Issue 1
  • DOI: 10.3390/v11010041

A pneumonia outbreak associated with a new coronavirus of probable bat origin
journal, February 2020


Extensive diversity of coronaviruses in bats from China
journal, July 2017