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PreprintCited by 87SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesGenomics and Phylogenetic Studies

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Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic

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Nelson, Chase W., Ardern, Zachary, Goldberg, Tony L., Meng, Chen, Kuo, Chen-Hao, Ludwig, Christina, Kolokotronis, Sergios-Orestis, Wei, Xinzhu·2020·eLife
DOI 10.1101/2020.05.21.109280PMC PMC7655111

Preprint — published as 10.7554/elife.59633 · Paper page

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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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Metadata

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
openRxiv
Published
2020-05-22
Volume
9
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2020.05.21.109280
PMC
PMC7655111
OpenAlex
W3091283230
Cited by
87
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 10 · 2023: 16 · 2022: 23 · 2021: 32 · 2020: 3
FWCI
2.42
Type
journal article
Language
en
Open access
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
  • National Science Foundation (1755370, 1758800)
  • National Philanthropic Trust
  • University of California Berkeley
  • University of Wisconsin-Madison
  • Academia Sinica
  • Division of Integrative Organismal Systems
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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