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Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2

View ORCID ProfileYvonne CF Su, Danielle E Anderson, Barnaby E Young, Feng Zhu, Martin Linster, Shirin Kalimuddin, Jenny GH Low, Zhuang Yan, Jayanthi Jayakumar, Louisa Sun, Gabriel Z Yan, Ian H Mendenhall, Yee-Sin Leo, David Chien Lye, Lin-Fa Wang, View ORCID ProfileGavin JD Smith
doi: https://doi.org/10.1101/2020.03.11.987222
Yvonne CF Su
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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  • ORCID record for Yvonne CF Su
Danielle E Anderson
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Barnaby E Young
2National Centre for Infectious Diseases
3Tan Tock Seng Hospital
9Lee Kong Chian School of Medicine
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Feng Zhu
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Martin Linster
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Shirin Kalimuddin
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
4Singapore General Hospital
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Jenny GH Low
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
4Singapore General Hospital
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Zhuang Yan
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Jayanthi Jayakumar
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Louisa Sun
5Alexandra Hospital
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Gabriel Z Yan
6National University Hospital
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Ian H Mendenhall
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
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Yee-Sin Leo
2National Centre for Infectious Diseases
3Tan Tock Seng Hospital
7Saw Swee Hock School of Public Health
8Yong Loo Lin School of Medicine
9Lee Kong Chian School of Medicine
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David Chien Lye
2National Centre for Infectious Diseases
3Tan Tock Seng Hospital
8Yong Loo Lin School of Medicine
9Lee Kong Chian School of Medicine
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Lin-Fa Wang
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
10SingHealth Duke-NUS Global Health Institute, Singapore
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  • For correspondence: linfa.wang@duke-nus.edu.sg gavin.smith@duke-nus.edu.sg
Gavin JD Smith
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School
10SingHealth Duke-NUS Global Health Institute, Singapore
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  • ORCID record for Gavin JD Smith
  • For correspondence: linfa.wang@duke-nus.edu.sg gavin.smith@duke-nus.edu.sg
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Abstract

To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.

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Posted March 12, 2020.
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Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2
Yvonne CF Su, Danielle E Anderson, Barnaby E Young, Feng Zhu, Martin Linster, Shirin Kalimuddin, Jenny GH Low, Zhuang Yan, Jayanthi Jayakumar, Louisa Sun, Gabriel Z Yan, Ian H Mendenhall, Yee-Sin Leo, David Chien Lye, Lin-Fa Wang, Gavin JD Smith
bioRxiv 2020.03.11.987222; doi: https://doi.org/10.1101/2020.03.11.987222
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Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2
Yvonne CF Su, Danielle E Anderson, Barnaby E Young, Feng Zhu, Martin Linster, Shirin Kalimuddin, Jenny GH Low, Zhuang Yan, Jayanthi Jayakumar, Louisa Sun, Gabriel Z Yan, Ian H Mendenhall, Yee-Sin Leo, David Chien Lye, Lin-Fa Wang, Gavin JD Smith
bioRxiv 2020.03.11.987222; doi: https://doi.org/10.1101/2020.03.11.987222

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