|
Basic Characteristics of Mutations
|
|
Mutation Site
|
R203K |
|
Mutation Site Sentence
|
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. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
N |
|
Standardized Encoding Gene
|
N
|
|
Genotype/Subtype
|
B.1.1;B.1.1.7 |
|
Viral Reference
|
NC_045512.2
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
UK |
|
Literature Information
|
|
PMID
|
34541432
|
|
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
|
|
Author
|
Leary S,Gaudieri S,Parker MD,Chopra A,James I,Pakala S,Alves E,John M,Lindsey BB,Keeley AJ,Rowland-Jones SL,Swanson MS,Ostrov DA,Bubenik JL,Das SR,Sidney J,Sette A,de Silva TI,Phillips E,Mallal S
|
|
Journal
|
Pathogens & immunity
|
|
Journal Info
|
2021 Aug 20;6(2):27-49
|
|
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 3 adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence 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.
|
|
Sequence Data
|
-
|
|
|