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

Chase W. NelsonXinzhu Wei


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.


Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P K Keese, A Gibbs
Feb 3, 2005·Genome Research·Chuong B DoSerafim Batzoglou
Apr 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·William R AtchleyTanja Drüke
Mar 1, 2006·Virus Research·Alexander E GorbalenyaEric J Snijder
Sep 16, 2006·Science·Edward C HolmesJonathan W Yewdell
Jan 24, 2008·BMC Immunology·John SidneyAlessandro Sette
Oct 8, 2009·Bioinformatics·Jacob F DegnerJonathan K Pritchard
Mar 17, 2010·BMC Bioinformatics·Andrew S WarrenJoão Carlos Setubal
May 20, 2011·Nature·Björn SchwanhäusserMatthias Selbach
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
May 24, 2012·Molecular Biology and Evolution·Julien SoubrierAlan Cooper
Nov 14, 2012·Annual Review of Genetics·Matthew D Daugherty, Harmit S Malik
Jan 19, 2013·Molecular Biology and Evolution·Kazutaka Katoh, Daron M Standley
Aug 21, 2013·PLoS Computational Biology·Michael LawrenceVincent J Carey
Apr 15, 2014·Bioinformatics·Wanding ZhouKen Chen
Nov 6, 2014·Molecular Biology and Evolution·Lam-Tung NguyenBui Quang Minh
Dec 8, 2014·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Chase W Nelson, Austin L Hughes
Jan 2, 2015·Genome Biology and Evolution·Xinzhu Wei, Jianzhi Zhang
Mar 13, 2016·BMC Bioinformatics·Melanie SchirmerChristopher Quince
Aug 2, 2016·Current Protocols in Immunology·Sinu PaulBjoern Peters
Sep 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Elodie CassanOlivier Gascuel
Oct 25, 2016·Trends in Microbiology·Diego ForniManuela Sironi
Nov 4, 2016·Nature Protocols·Stefka TyanovaJuergen Cox
Sep 10, 2017·Trends in Genetics : TIG·Lorenzo Calviello, Uwe Ohler
Oct 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vanessa JurtzMorten Nielsen
Jul 19, 2018·Bioinformatics·Ben LangmeadRone Charles
Aug 14, 2018·Molecular Biology and Evolution·Timothy E SchlubEdward C Holmes
Dec 12, 2018·Nature Reviews. Microbiology·Jie CuiZheng-Li Shi
Feb 1, 2020·The New England Journal of Medicine·Camilla RotheMichael Hoelscher
Mar 4, 2020·Nature Microbiology·UNKNOWN Coronaviridae Study Group of the International Committee on Taxonomy of Viruses

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