Literature detail

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

Xiaojun Li¹ Elena E Giorgi² Manukumar Honnayakanahalli Marichannegowda¹ Brian Foley² Chuan Xiao³ Xiang-Peng Kong⁴ Yue Chen¹ S Gnanakaran² Bette Korber^2,5 Feng Gao^6,7

Affiliations 7 institutions

Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, TX 79968, USA.
Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University, New York, NY 10016, USA.
New Mexico Consortium, Los Alamos, NM 87545, USA.
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. [email protected].
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.

PMID 32937441 2020 Sci Adv eng epublish

PubMed DOI Browse context

Article

Publication summary

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.

Recombination, Genetic Amino Acid Sequence Angiotensin-Converting Enzyme 2 Animals Betacoronavirus Binding Sites Chiroptera Coronavirus Infections COVID-19 Evolution, Molecular Genome, Viral Humans Pandemics Peptidyl-Dipeptidase A Phylogeny Pneumonia, Viral Protein Structure, Tertiary SARS-CoV-2

Structured evidence records

Evidence records

4 total

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.90

Key finding

Strong purifying selection around the spike receptor binding motif indicates conserved molecular adaptation of SARS-CoV-2-related coronaviruses across bat, pangolin, and human hosts.

Virus

Host

Location

Supporting text

Genes or proteins: spike
Receptors: receptor binding motif
Mechanism types: receptor_binding; molecular_conservation

Molecular Adaptation Extraction confidence 0.90

Key finding

Recombination of the spike receptor binding motif from pangolin coronaviruses contributed to SARS-CoV-2 adaptation enabling human infection.

Virus

Host

Location

Supporting text

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.

Genes or proteins: spike
Receptors: receptor binding motif
Mechanism types: recombination; receptor_binding; host_adaptation

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.95

Key finding

Sequence comparisons and phylogenetic analysis revealed that SARS-CoV-2 acquired its receptor binding motif through recombination with pangolin coronaviruses and underwent strong purifying selection in bat, pangolin, and human hosts.

Virus

Host

Location

Supporting text

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.

Genes or proteins: spike; receptor binding motif
Analysis methods: sequence alignment; phylogenetic analysis; comparative genomics

Recombination Or Reassortment 1 records

Recombination Or Reassortment Extraction confidence 1.00

Key finding

SARS-CoV-2 acquired its receptor binding motif through recombination with pangolin coronaviruses, which may have facilitated adaptation to humans.

Virus

Host

Location

Supporting text

Event type: recombination
Genes or segments: receptor binding motif; spike

Citation context

References

50 references

Reference network

Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.

260 nodes · 423 links · capped

Drag nodes to explore citation neighborhoods


PMID 31978945	F., Tan W.; for the China Novel Coronavirus Investigating and Research Team , A novel coronavirus from patients with pneumonia in China, 2019. N. Engl	Zhu	2020
-	Organization, Novel Coronavirus (COVID-19) Situation (2020);	W	2020
PMID 32015508 In OmniVira	A new coronavirus associated with human respiratory disease in China.	Wu	2020
PMID 32123347	Nat	Coronaviridae Study Group of the Interna	2020
PMID 30531947	L., Origin and evolution of pathogenic coronaviruses	Cui	2019
PMID 28384506	C., Zhang Y.-Z., Extensive diversity of coronaviruses in bats from China. Virology 507, 1–10 (2017)	Lin	2017
PMID 30634396	, Kulcsar K	Banerjee	2019
PMID 32015507	, Yang X	Zhou	2020
PMID 32007145 In OmniVira	Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.	Lu	2020
PMID 32218527 In OmniVira	Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.	Lam	2020
PMID 31652964	, Chen W	Liu	2019
PMID 19906932	L., Baric R. S., Recombination, reservoirs, and the modular spike: Mechanisms of coronavirus cross-species transmission	Graham	2010
PMID 32210130	U., Shafique L., Ihsan A., Liu Q., Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens 9, 240 (2020)	Rehman	2020
PMID 12958366	J., He Y. Q., Liu X. L., Zhuang Z. X., Cheung C. L., Luo S. W., Li P. H., Zhang L	Guan	2003
PMID 24896817	I., El-Kafrawy S. A., Farraj S. A., Hassan A. M., Al-Saeed M. S., Hashem A. M., Madani T. A., Evidence for camel-to-human transmission of MERS coronavirus. N. Engl	Azhar	2014
PMID 9847317	S., Bollinger R. C., Paranjape R. S., Gadkari D., Kulkarni S. S., Novak N. G., Ingersoll R., Sheppard H. W., Ray S. C., Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination	Lole	1999
-	C., Javornik Cregeen S	Wong	2020
PMID 8573400	C., Halpern A. L., Macken C., Korber B. T., A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences	Siepel	1995
PMID 27578435	, Structure, function, and evolution of coronavirus spike proteins	Li	2016
PMID 32155444 In OmniVira	Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.	Walls	2020
PMID 29190287	, Zeng L	Hu	2017
PMID 32094589	, Marzi A	Letko	2020
PMID 14647384	J., Vasilieva N., Sui J., Wong S. K., Berne M. A., Somasundaran M., Sullivan J. L., Luzuriaga K., Greenough T. C., Choe H., Farzan M., Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus	Li	2003
PMID 32225176 In OmniVira	Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.	Lan	2020
PMID 32075877 In OmniVira	Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.	Wrapp	2020
PMID 32225175 In OmniVira	Structural basis of receptor recognition by SARS-CoV-2.	Shang	2020
PMID 32056509	, Li X	Xiao	2020
PMID 32284615	G., Rambaut A., Lipkin W. I., Holmes E. C., Garry R. F., The proximal origin of SARS-CoV-2	Andersen	2020
PMID 32057769	G., Decroly E., The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade	Coutard	2020
-	C., Hughes A. C., Bi Y., Shi W., A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19. bioRxiv, 2020.2003.2002.974139 (2020)	Zhou	2020
PMID 32231345	, Liu M	Xia	2020
PMID 32311094	Brufsky, Distinct viral clades of SARS-CoV-2: Implications for modeling of viral spread	A	2020
PMID 18057240	J., Yip C.-W., Zeng F., Lam P.-Y., Leung F. C.-C., Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus	Hon	2008
PMID 26269185	P., Feng Y., Chen H., Luk H. K. H., Yang W.-H., Li K. S. M., Zhang Y.-Z., Huang Y., Song Z.-Z., Chow W.-N., Fan R. Y. Y., Ahmed S. S., Yeung H. C., Lam C. S. F., Cai J.-P., Wong S. S. Y., Chan J. F. W., Yuen K.-Y., Zhang H.-L., Woo P. C. Y., Severe acute respiratory syndrome (SARS) coronavirus ORF8 protein is acquired from SARS-related coronavirus from greater horseshoe bats through recombination	Lau	2015
PMID 31987001 In OmniVira	Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan.	Chan	2020
PMID 28382917	, McCauley J	Shu	2017
PMID 31565258	, Buckland-Merrett G	Elbe	2017
PMID 26552008 In OmniVira	A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.	Menachery	2015
PMID 26976607	D., Yount B. L. Jr., Sims A. C., Debbink K., Agnihothram S. S., Gralinski L. E., Graham R. L., Scobey T., Plante J. A., Royal S. R., Swanstrom J., Sheahan T. P., Pickles R	Menachery	2016
PMID 24172901	A., Zhu G., Epstein J. H., Mazet J. K., Hu B., Zhang W., Peng C., Zhang Y.-J., Luo C.-M., Tan B., Wang N., Zhu Y., Crameri G., Zhang S.-Y., Wang L.-F., Daszak P., Shi Z.-L., Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor	Ge	2013
PMID 29500691	A., Hagan E., Zhou J.-H., Zhang Y.-Z., Wang L.-F., Daszak P., Shi Z.-L., Serological evidence of bat SARS-related coronavirus infection in humans, China	Wang	2018
-	Jiang, X.-F. Wan, Y. Hua, X. Wang, F. Hou, J. Chen, J. Zou, J. Chen, Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV)? bioRxiv , 2020.2002.2018.954628 (2020); 10.1101/2020.02.18.954628	P	2020
-	A., Hagan E., Zhou J.-H., Zhang Y.-Z., Wang L.-F., Daszak P., Shi Z.-L., Isolation and characterization of 2019-nCoV-like coronavirus from Malayan pangolins. bioRxiv, 2020.2002.2017.951335 (2020)	Wang	2020
PMID 17846036	A., Blackshields G., Brown N. P., Chenna R., McGettigan P. A., McWilliam H., Valentin F., Wallace I. M., Wilm A., Lopez R., Thompson J. D., Gibson T	Larkin	2007
PMID 14530136	, Gascuel O	Guindon	2003
-	Foley et al	B	2018
-	Korber, in Computational Analysis of HIV Molecular Sequences , A. G. Rodrigo, G. H. Learn, Eds. (Kluwer Academic Publishers, Dordrecht, Netherlands, 2000), chap. 4, pp. 55–72	B	2000
PMID 15264254	F., Goddard T. D., Huang C. C., Couch G. S., Greenblatt D. M., Meng E. C., Ferrin T. E., UCSF Chimera--a visualization system for exploratory research and analysis	Pettersen	2004
PMID 26678386	, Zhang Y	Yang	2015
-	, Totrov M	Abagyan	1994

Evidence overview

Evidence 4

Types 3

Virus 2

Host 3

Evidence types

Molecular Adaptation 2 Genomic Evolution 1 Recombination Or Reassortment 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Science advances
Volume / Issue / Pages: 6 / 27 / -
ISSN: 2375-2548
Journal country: United States
DOI: 10.1126/sciadv.abb9153