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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 (\u201cimperfect homologous recombination\u201d). 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\u2019 and 3\u2019 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 \u201carms\u201d 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.<\/jats:p>","DOI":"10.1186\/s13040-021-00251-0","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T13:02:44Z","timestamp":1616245364000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Indels in SARS-CoV-2 occur at template-switching hotspots"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7157-607X","authenticated-orcid":false,"given":"Brianna Sierra","family":"Chrisman","sequence":"first","affiliation":[]},{"given":"Kelley","family":"Paskov","sequence":"additional","affiliation":[]},{"given":"Nate.","family":"Stockham","sequence":"additional","affiliation":[]},{"given":"Kevin","family":"Tabatabaei","sequence":"additional","affiliation":[]},{"given":"Jae-Yoon","family":"Jung","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Washington","sequence":"additional","affiliation":[]},{"given":"Maya","family":"Varma","sequence":"additional","affiliation":[]},{"given":"Min Woo","family":"Sun","sequence":"additional","affiliation":[]},{"given":"Sepideh","family":"Maleki","sequence":"additional","affiliation":[]},{"given":"Dennis P.","family":"Wall","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"issue":"6","key":"251_CR1","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1111\/mec.15066","volume":"28","author":"M Wellenreuther","year":"2019","unstructured":"Wellenreuther M, M\u00e9rot C, Berdan E, Bernatchez L. 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