scholarly journals 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

2021 ◽  
Vol 6 (2) ◽  
pp. 27-49
Author(s):  
Shay Leary ◽  
Silvana Gaudieri ◽  
Matthew Parker ◽  
Abha Chopra ◽  
Ian James ◽  
...  

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.

2012 ◽  
Vol 40 (16) ◽  
pp. 7633-7643 ◽  
Author(s):  
Chikako Ragan ◽  
Bryan J. Mowry ◽  
Denis C. Bauer

2012 ◽  
Vol 5 (1) ◽  
pp. 338
Author(s):  
Sharon Ben-Zvi ◽  
Adi Givati ◽  
Noam Shomron

2017 ◽  
Vol 26 ◽  
pp. 1-11 ◽  
Author(s):  
Molly M. Rathbun ◽  
Jennifer A. McElhoe ◽  
Walther Parson ◽  
Mitchell M. Holland

Biology ◽  
2012 ◽  
Vol 1 (2) ◽  
pp. 297-310 ◽  
Author(s):  
Xiaozeng Yang ◽  
Lei Li

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e16403 ◽  
Author(s):  
Seongho Ryu ◽  
Natasha Joshi ◽  
Kevin McDonnell ◽  
Jongchan Woo ◽  
Hyejin Choi ◽  
...  

2016 ◽  
Vol 37 (12) ◽  
pp. 1283-1298 ◽  
Author(s):  
Dario Veneziano ◽  
Sebastiano Di Bella ◽  
Giovanni Nigita ◽  
Alessandro Laganà ◽  
Afredo Ferro ◽  
...  

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