RT Journal Article
SR Electronic
T1 Structural Variants in SARS-CoV-2 Occur at Template-Switching Hotspots
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.01.278952
DO 10.1101/2020.09.01.278952
A1 Brianna Chrisman
A1 Kelley Paskov
A1 Nate Stockham
A1 Kevin Tabatabaei
A1 Jae-Yoon Jung
A1 Peter Washington
A1 Maya Varma
A1 Min Woo Sun
A1 Sepideh Maleki
A1 Dennis P. Wall
YR 2020
UL http://biorxiv.org/content/early/2020/09/02/2020.09.01.278952.abstract
AB 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 structural variants (SVs) 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 imperfect homologous recombination between SARS-CoV-2 replicates, and provide four independent pieces of evidence. (1) The SVs 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 structural variant hotspots have cases of both high intra-host heterogeneity and intra-host homogeneity, suggesting that these structural variants are both consequences of de novo recombination events within a host and artifacts of previous recombination. (4) Within the RNA secondary structure, the indels occur in “arms” 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.