Indels in SARS-CoV-2 occur at template-switching hotspots
| Autor: | Peter Washington, Maya Varma, Min Woo Sun, Jae-Yoon Jung, Sepideh Maleki, Kevin Tabatabaei, Nate Tyler Stockham, Dennis P. Wall, Brianna Chrisman, Kelley Paskov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
RNA virus
viruses lcsh:Analysis lcsh:Computer applications to medicine. Medical informatics Biochemistry Nucleic acid secondary structure Structural variation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine RNA polymerase Genetics Consensus sequence Indel Molecular Biology 030304 developmental biology 0303 health sciences biology SARS-CoV-2 Research lcsh:QA299.6-433 RNA food and beverages Genomics biology.organism_classification Recombination Computer Science Applications Computational Mathematics Computational Theory and Mathematics chemistry Evolutionary biology lcsh:R858-859.7 Homologous recombination 030217 neurology & neurosurgery |
| Zdroj: | BioData Mining BioData Mining, Vol 14, Iss 1, Pp 1-16 (2021) |
| ISSN: | 1756-0381 |
| Popis: | The evolutionary dynamics of SARS-CoV-2 have been carefully monitored since the COVID-19 pandemic began in December 2019. However, analysis has focused primarily on single nucleotide polymorphisms and largely ignored the role of insertions and deletions (indels) as well as recombination in SARS-CoV-2 evolution. Using sequences from the GISAID database, we catalogue over 100 insertions and deletions in the SARS-CoV-2 consensus sequences. We hypothesize that these indels are artifacts of recombination events between SARS-CoV-2 replicates whereby RNA-dependent RNA polymerase (RdRp) re-associates with a homologous template at a different loci (“imperfect homologous recombination”). We provide several independent pieces of evidence that suggest this. (1) The indels from the GISAID consensus sequences are clustered at specific regions of the genome. (2) These regions are also enriched for 5’ and 3’ breakpoints in the transcription regulatory site (TRS) independent transcriptome, presumably sites of RNA-dependent RNA polymerase (RdRp) template-switching. (3) Within raw reads, these indel hotspots have cases of both high intra-host heterogeneity and intra-host homogeneity, suggesting that these indels are both consequences of de novo recombination events within a host and artifacts of previous recombination. We briefly analyze the indels in the context of RNA secondary structure, noting that indels preferentially occur in “arms” and loop structures of the predicted folded RNA, suggesting that secondary structure may be a mechanism for TRS-independent template-switching in SARS-CoV-2 or other coronaviruses. These insights into the relationship between structural variation and recombination in SARS-CoV-2 can improve our reconstructions of the SARS-CoV-2 evolutionary history as well as our understanding of the process of RdRp template-switching in RNA viruses. Supplementary Information The online version contains supplementary material available at (10.1186/s13040-021-00251-0). |
| Databáze: | OpenAIRE |
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