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Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level
bioRxiv: The preprint server for Biology
Cold Spring Habor Laboratory
2021
Abstract
Background Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over-time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally.
Methods Deep sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome.
Results Sequence analysis suggests that the three adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS) rather than by stepwise mutation. The resulting sequence changes generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain of nucleocapsid. Deep sequencing data from 981 clinical samples confirmed the presence of the novel TRS-CS-dimerization domain RNA in individuals with the K203/R204 variant. Quantification of sub-genomic RNA indicates that viruses with the K203/R204 variant may also have increased expression of sub-genomic RNA from other open reading frames.
Conclusions The finding that homologous recombination from the TRS may have occurred since the introduction of SARS-CoV-2 in humans resulting in both coding changes and novel sub-genomic RNA transcripts suggests this as a mechanism for diversification and adaptation within its new host.
Details
- Title
- Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level
- Authors/Creators
- S. Leary (Author/Creator) - Murdoch UniversityS. Gaudieri (Author/Creator) - Vanderbilt University Medical CenterM.D. Parker (Author/Creator) - University of SheffieldA. Chopra (Author/Creator) - Murdoch UniversityI. James (Author/Creator) - Murdoch UniversityS. Pakala (Author/Creator) - Vanderbilt University Medical CenterE. Alves (Author/Creator) - The University of Western AustraliaM. John (Author/Creator) - Royal Perth HospitalB.B. Lindsey (Author/Creator) - InteracA.J. Keeley (Author/Creator) - InteracS.L. Rowland-Jones (Author/Creator) - InteracM.S. Swanson (Author/Creator) - University of FloridaD.A. Ostrov (Author/Creator) - University of FloridaJ.L. Bubenik (Author/Creator) - University of FloridaS. Das (Author/Creator) - Vanderbilt University Medical CenterJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyA. Sette (Author/Creator) - La Jolla Institute for ImmunologyT.I. de Silva (Author/Creator) - InteracE. Phillips (Author/Creator) - Vanderbilt University Medical CenterS. Mallal (Author/Creator) - Vanderbilt University Medical Center
- Publication Details
- bioRxiv: The preprint server for Biology
- Publisher
- Cold Spring Habor Laboratory
- Identifiers
- 991005541752907891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Other
- Additional Information
- Others included in authorship are part of the COVID-19 Genomics UK (COG-UK) consortium
- Resource Sub-type
- Nonrefereed Article
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