. 2022 Aug 26;377(6609):960-966.

doi: 10.1126/science.abp8337. Epub 2022 Jul 26.

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Jonathan E Pekar^{1

2}, Andrew Magee³, Edyth Parker⁴, Niema Moshiri⁵, Katherine Izhikevich^{5

6}, Jennifer L Havens¹, Karthik Gangavarapu³, Lorena Mariana Malpica Serrano⁷, Alexander Crits-Christoph⁸, Nathaniel L Matteson⁴, Mark Zeller⁴, Joshua I Levy⁴, Jade C Wang⁹, Scott Hughes⁹, Jungmin Lee¹⁰, Heedo Park^{10

11}, Man-Seong Park^{10

11}, Katherine Ching Zi Yan¹², Raymond Tzer Pin Lin¹², Mohd Noor Mat Isa¹³, Yusuf Muhammad Noor¹³, Tetyana I Vasylyeva¹⁴, Robert F Garry^{15

16

17}, Edward C Holmes¹⁸, Andrew Rambaut¹⁹, Marc A Suchard^{3

20

21}, Kristian G Andersen^{4

22}, Michael Worobey⁷, Joel O Wertheim¹⁴

Affiliations

¹ Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
² Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA 92093, USA.
³ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁵ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ Department of Mathematics, University of California, San Diego, La Jolla, CA 92093, USA.
⁷ Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.
⁸ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁹ New York City Public Health Laboratory, New York City Department of Health and Mental Hygiene, New York, NY 11101, USA.
¹⁰ Department of Microbiology, Institute for Viral Diseases, Biosafety Center, College of Medicine, Korea University, Seoul, South Korea.
¹¹ BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea.
¹² National Public Health Laboratory, National Centre for Infectious Diseases, Singapore.
¹³ Malaysia Genome and Vaccine Institute, Jalan Bangi, 43000 Kajang, Selangor, Malaysia.
¹⁴ Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁵ Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁶ Zalgen Labs, Frederick, MD 21703, USA.
¹⁷ Global Virus Network (GVN), Baltimore, MD 21201, USA.
¹⁸ Sydney Institute for Infectious Diseases, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁹ Institute of Evolutionary Biology, University of Edinburgh, King's Buildings, Edinburgh EH9 3FL, UK.
²⁰ Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
²¹ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
²² Scripps Research Translational Institute, La Jolla, CA 92037, USA.

PMID: 35881005
PMCID: PMC9348752
DOI: 10.1126/science.abp8337

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Jonathan E Pekar et al. Science. 2022.

. 2022 Aug 26;377(6609):960-966.

doi: 10.1126/science.abp8337. Epub 2022 Jul 26.

Authors

Affiliations

¹ Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
² Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA 92093, USA.
³ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁵ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ Department of Mathematics, University of California, San Diego, La Jolla, CA 92093, USA.
⁷ Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.
⁸ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁹ New York City Public Health Laboratory, New York City Department of Health and Mental Hygiene, New York, NY 11101, USA.
¹⁰ Department of Microbiology, Institute for Viral Diseases, Biosafety Center, College of Medicine, Korea University, Seoul, South Korea.
¹¹ BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea.
¹² National Public Health Laboratory, National Centre for Infectious Diseases, Singapore.
¹³ Malaysia Genome and Vaccine Institute, Jalan Bangi, 43000 Kajang, Selangor, Malaysia.
¹⁴ Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁵ Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁶ Zalgen Labs, Frederick, MD 21703, USA.
¹⁷ Global Virus Network (GVN), Baltimore, MD 21201, USA.
¹⁸ Sydney Institute for Infectious Diseases, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁹ Institute of Evolutionary Biology, University of Edinburgh, King's Buildings, Edinburgh EH9 3FL, UK.
²⁰ Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
²¹ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
²² Scripps Research Translational Institute, La Jolla, CA 92037, USA.

PMID: 35881005
PMCID: PMC9348752
DOI: 10.1126/science.abp8337

Erratum in

Erratum for the Research Article "The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2" by J. E. Pekar et al.
[No authors listed] [No authors listed] Science. 2023 Oct 13;382(6667):eadl0585. doi: 10.1126/science.adl0585. Epub 2023 Oct 13. Science. 2023. PMID: 37824677 No abstract available.

Abstract

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

PubMed Disclaimer

Figures

**Fig. 1.. Maximum likelihood phylogeny of the early SARS-CoV-2 pandemic, showing nucleotide reversions and putative candidates for the ancestral haplotype at the most common recent ancestor (MRCA).**
Putative ancestral haplotypes are identified with colored shapes. Reversions from the Hu-1 reference genotype to the recCA are colored. Blue represents C-to-T reversions and black indicates all other reversions. The tree is rooted on Hu-1 to show reversion dynamics to the recCA.

**Fig. 2.. Probability of phylogenetic structures arising from a single introduction of SARS-CoV-2 in epidemic simulations.**
(A) A large polytomy of at least 20 descendent lineages, consistent with the base of both lineages A and B. (B) Topology matching a C/C ancestral haplotype: two clades each one mutation from the ancestor, both with polytomies of at least 20 descendent lineages. (C) Topology matching either a lineage A or lineage B ancestral haplotype: a basal polytomy with at least 20 descendent lineages including a large clade separated by two mutations, also possessing a polytomy of at least 20 descendent lineages. Basal taxa have short branch lengths for clarity. The probability of each phylogenetic structure after a single introduction is reported in the box.

**Fig. 3.. Comparison of the tMRCA and primary case dates for lineage A and lineage B across rooting strategies.**
Each row represents a different rooting constraint in phylodynamic analysis, with lineage B, C/C and lineage A representing a fixed ancestral haplotype. (A) The tMRCA for lineages A and B. (B) The number of weeks the tMRCA of lineage A occurs after the tMRCA of lineage B. (C) The timing of the primary case for lineages A and B. (D) The number of weeks the time of the primary case of lineage A occurs after the time of the primary case of lineage B. Long dashed lines indicate the median and shading represents the 95% HPD for each distribution. Short dashed lines indicate 0 weeks difference between lineages A and B. Posterior probability that lineage A originated after lineage B is reported in the grey box.

**Fig. 4.. Dynamics of simulated SARS-CoV-2 epidemics resulting from separate introductions of lineages A and B.**
Each row represents a different rooting constraint in phylodynamic analysis, with lineage B, C/C and lineage A representing a fixed ancestral haplotype. (A) Estimated number of infections. The header of each column indicates whether the number of infections are caused by lineage A, lineage B, or the two lineages combined. Darker and lighter shading represent the 50% and 95% HPD, respectively. (B) The log ratio of lineage B to lineage A infections on 15 December 2019. Posterior probability of having more lineage B infections than lineage A reported in the grey box.

See this image and copyright information in PMC

Comment in

Wildlife trade is likely the source of SARS-CoV-2.
Jiang X, Wang R. Jiang X, et al. Science. 2022 Aug 26;377(6609):925-926. doi: 10.1126/science.add8384. Epub 2022 Aug 25. Science. 2022. PMID: 36007033

References

1. Dong E., Du H., Gardner L., An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 20, 533–534 (2020). 10.1016/S1473-3099(20)30120-1 - DOI - PMC - PubMed
1. Ren L.-L., Wang Y.-M., Wu Z.-Q., Xiang Z.-C., Guo L., Xu T., Jiang Y.-Z., Xiong Y., Li Y.-J., Li X.-W., Li H., Fan G.-H., Gu X.-Y., Xiao Y., Gao H., Xu J.-Y., Yang F., Wang X.-M., Wu C., Chen L., Liu Y.-W., Liu B., Yang J., Wang X.-R., Dong J., Li L., Huang C.-L., Zhao J.-P., Hu Y., Cheng Z.-S., Liu L.-L., Qian Z.-H., Qin C., Jin Q., Cao B., Wang J.-W., Identification of a novel coronavirus causing severe pneumonia in human: A descriptive study. Chin. Med. J. (Engl.) 133, 1015–1024 (2020). 10.1097/CM9.0000000000000722 - DOI - PMC - PubMed
1. H. Ritchie, E. Mathieu, L. Rodés-Guirao, C. Appel, C. Giattino, E. Ortiz-Ospina, J. Hasell, B. Macdonald, S. Beltekian, X. Roser, Coronavirus Pandemic (COVID-19). Our World in Data (2022); https://ourworldindata.org/covid-deaths.
1. Rambaut A., Holmes E. C., O’Toole Á., Hill V., McCrone J. T., Ruis C., du Plessis L., Pybus O. G., A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat. Microbiol. 5, 1403–1407 (2020). 10.1038/s41564-020-0770-5 - DOI - PMC - PubMed
1. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y., Wang Q.-M., Zheng J.-J., Xu L., Holmes E. C., Zhang Y.-Z., A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). 10.1038/s41586-020-2008-3 - DOI - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- ImmPort - Shared Data - Datasets
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Affiliations

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Authors

Affiliations

Erratum in

Abstract

Figures

Comment in

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous