key: cord-0955522-y70kj7x6 authors: Bartas, Martin; Goswami, Pratik; Lexa, Matej; Červeň, Jiří; Volná, Adriana; Fojta, Miroslav; Brázda, Václav; Pečinka, Petr title: Letter to the Editor: Significant mutation enrichment in inverted repeat sites of new SARS-CoV-2 strains date: 2021-04-09 journal: Brief Bioinform DOI: 10.1093/bib/bbab129 sha: 43130d0da149808f5320758db253484649ef5956 doc_id: 955522 cord_uid: y70kj7x6 In a recently published paper, we have found that SARS-CoV-2 hot-spot mutations are significantly associated with inverted repeat loci and CG dinucleotides. However, fast-spreading strains with new mutations (so-called mink farm mutations, England mutations and Japan mutations) have been recently described. We used the new datasets to check the positioning of mutation sites in genomes of the new SARS-CoV-2 strains. Using an open-access Palindrome analyzer tool, we found mutations in these new strains to be significantly enriched in inverted repeat loci. . Relative percentual enrichment of SARS-CoV-2 mutational datasets within IRs. The assumption is that there is no enrichment of IRs within SARS-CoV-2 hotspots (zero value in the plot). A one-sample t-test was used to statistically compare the number of real SARS-CoV-2 mutations within IRs with random mutations localization (done in 100 replicates). * * * indicates P-value < 0.001. Detailed information can be found in [1] . of the different B.1.1.28 clades detected in Brazil and Japan (11 January 2021) [4] . We have analyzed these new datasets of SARS-CoV-2 mutations by the Palindrome analyzer [5] and found a remarkably high and statistically significant (P-value < 2.2e−16) enrichment of mutations within the IRs in all three new SARS-CoV-2 strains (Figure 1 ). If we consider only the longer IRs (7+ nucleotides), the observed enrichment is even two-times higher (for all analyzed mutational datasets and overlays of IRs with tested mutations, see Supplementary Data available online at https://academic.oup.com/bib). It is therefore evident that inverted repeat loci play an important role in SARS-CoV-2 genetic drift and should be extra monitored by predictive analyses and modelling. Our dataset is also in line with previously published data [6] saying that SARS-CoV-2 mutations are strongly biased toward C > U and U> C transitions (32 out of 67 analyzed mutations; 47.8% of all SARS-CoV-2 mutations in the novel datasets belong to C > U + U > C transitions, while the expected value is slightly above 15% for C > U + U > C in the SARS-CoV-2 genome [6] ). • We have analyzed three novel datasets of SARS-CoV-2 hot-spot mutations. • IRs are a rich source of SARS-CoV-2 genetic instability. • These novel results can be further utilized for predictive analyses of further possible SARS-CoV-2 mutations. Supplementary data are available online at https://academi c.oup.com/bib. The Czech Science Foundation (18-15548S, 18-18699S); and the SYMBIT project Reg. no. CZ.02.1.01/0.0/0.0/15_003/ 0000477 financed from the ERDF. SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein Palindrome analyser-a new web-based server for predicting and evaluating inverted repeats in nucleotide sequences Mutation patterns of human SARS-CoV-2 and bat RaTG13 coronavirus genomes are strongly biased towards C > U transitions, indicating rapid evolution in their hosts All data are available in the paper and in the Supplementary data.