Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic
- Academia Sinica, Taiwan
- Technical University of Munich, Germany
- University of Wisconsin-Madison, United States
- American Museum of Natural History, United States
- University of California, Berkeley, United States
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supplement. Scripts and source data for all analyses and figures are provided on GitHub at https://github.com/chasewnelson/SARS-CoV-2-ORF3d and Zenodo at https://zenodo.org/record/4052729.
-
Proteome and Translatome of SARS-CoV-2 infected cellsPRIDE database, PXD017710.
-
Vero cells infected with SARS CoV 2 no quantitation slices 1-10 of 20; vero cells infected with SARS CoV2 slices 11-20 of 20 slicesZenodo, 10.5281/zenodo.3722590, 10.5281/zenodo.3722596.
-
Proteomics of SARS-CoV and SARS-CoV-2 infected cellsPRIDE database, PXD018581.
-
Decoding SARS-CoV-2 coding capacityGEO database, sample IDs: SRR11713366, SRR11713367, SRR11713368, SRR11713369 from GSE149973.
-
Assays and Merits of Proteomics for SARS-CoV-2 Research and TestingPRIDE database, PXD019645.
Article and author information
Author details
Sergios-Orestis Kolokotronis
Funding
Academia Sinica (Postdoctoral Research Fellowship)
- Chase W Nelson
National Philanthropic Trust (Grant)
- Zachary Ardern
University of Wisconsin-Madison (John D. MacArthur Professorship Chair)
- Tony L Goldberg
National Science Foundation (IOS grants #1755370 and #1758800)
- Sergios-Orestis Kolokotronis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antonis Rokas, Vanderbilt University, United States
Publication history
- Received: June 3, 2020
- Accepted: September 30, 2020
- Accepted Manuscript published: October 1, 2020 (version 1)
- Version of Record published: November 10, 2020 (version 2)
Copyright
© 2020, Nelson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 16,280
- Page views
-
- 1,482
- Downloads
-
- 47
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic
eLife 9:e59633.
https://doi.org/10.7554/eLife.59633
Further reading
-
- Evolutionary Biology
The avian palaeognath phylogeny has been recently revised significantly due to the advancement of genome-wide comparative analyses and provides the opportunity to trace the evolution of the microstructure and crystallography of modern dinosaur eggshells. Here, eggshells of all major clades of Palaeognathae (including extinct taxa) and selected eggshells of Neognathae and non-avian dinosaurs are analysed with electron backscatter diffraction. Our results show the detailed microstructures and crystallographies of (previously) loosely categorized ostrich-, rhea-, and tinamou-style morphotypes of palaeognath eggshells. All rhea-style eggshell appears homologous, while respective ostrich-style and tinamou-style morphotypes are best interpreted as homoplastic morphologies (independently acquired). Ancestral state reconstruction and parsimony analysis additionally show that rhea-style eggshell represents the ancestral state of palaeognath eggshells both in microstructure and crystallography. The ornithological and palaeontological implications of the current study are not only helpful for the understanding of evolution of modern and extinct dinosaur eggshells, but also aid other disciplines where palaeognath eggshells provide useful archive for comparative contrasts (e.g. palaeoenvironmental reconstructions, geochronology, and zooarchaeology).
-
- Evolutionary Biology
Vertebrate limb morphology often reflects the environment due to variation in locomotor requirements. However, proximal and distal limb segments may evolve differently from one another, reflecting an anatomical gradient of functional specialization that has been suggested to be impacted by the timing of development. Here we explore whether the temporal sequence of bone condensation predicts variation in the capacity of evolution to generate morphological diversity in proximal and distal forelimb segments across more than 600 species of mammals. Distal elements not only exhibit greater shape diversity, but also show stronger within-element integration and, on average, faster evolutionary responses than intermediate and upper limb segments. Results are consistent with the hypothesis that late developing distal bones display greater morphological variation than more proximal limb elements. However, the higher integration observed within the autopod deviates from such developmental predictions, suggesting that functional specialization plays an important role in driving within-element covariation. Proximal and distal limb segments also show different macroevolutionary patterns, albeit not showing a perfect proximo-distal gradient. The high disparity of the mammalian autopod, reported here, is consistent with the higher potential of development to generate variation in more distal limb structures, as well as functional specialization of the distal elements.
