Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic
Open accessPublished version of a preprint
Abstract
Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes. Overlapping genes (OLGs) are common in viruses and have been associated with pandemics but are still widely overlooked. We identify and characterize ORF3d , a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not other closely related pangolin-CoVs or bat-CoVs. We then document evidence of ORF3d translation, characterize its protein sequence, and conduct an evolutionary analysis at three levels: between taxa (21 members of Severe acute respiratory syndrome-related coronavirus ), between human hosts (3978 SARS-CoV-2 consensus sequences), and within human hosts (401 deeply sequenced SARS-CoV-2 samples). ORF3d has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as the unrelated gene ORF3b , leading to confusion. Our results liken ORF3d to other accessory genes in emerging viruses and highlight the importance of OLGs.
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Cites
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- Authors
- Nelson, C. W., Ardern, Z., Goldberg, T. L., Meng, C., Kuo, C.-H., Ludwig, C., Kolokotronis, S.-O., & Wei, X.
- Affiliations
- American Museum of Natural History (US)
- Technical University of Munich (DE)
- University of Wisconsin–Madison (US)
- Biodiversity Research Center, Academia Sinica (TW)
- University of California, Los Angeles (US)
- Corresponding author
- Nelson, Chase W
- Ardern, Zachary
- Wei, Xinzhu
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-10-01
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7655111
- OpenAlex
- W3091283230
- Cited by
- 87
- References
- 5
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 10 · 2023: 16 · 2022: 23 · 2021: 32 · 2020: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by)
- Funders
- Academia Sinica (Postdoctoral Research Fellowship)
- National Philanthropic Trust (Grant)
- University of Wisconsin-Madison (John D MacArthur Professorship Chair)
- National Science Foundation (IOS grants #1755370 and #1758800)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- SARS-CoV-2, overlapping genes, accessory genes, pangolin coronavirus, bat coronaviruses, viral evolution, antibody response, COVID-19 pandemic
- MeSH terms
- Eutheria, Betacoronavirus, COVID-19, SARS-CoV-2, Amino Acid Sequence, Animals, Antibodies, Viral, Antibody Specificity, Epitopes, Antigens, Viral, China, Chiroptera, Europe, Genes, Overlapping, Genes, Viral, Haplotypes, Humans, Models, Molecular, Mutation, Phylogeny, Pneumonia, Viral, Protein Conformation, RNA, Viral, Sequence Homology, Nucleic Acid, Protein Biosynthesis, Genetic Variation, Viral Proteins, Gene Expression Regulation, Viral, Open Reading Frames, Sequence Alignment, Coronavirus, Coronavirus Infections, Evolution, Molecular, Host Specificity, Pandemics
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