RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses

Ramya Rangan; Ivan N. Zheludev; Rhiju Das

To further tighten this list of conserved sequences to ones most relevant to the current COVID-19 outbreak, we analyzed whether sequence regions conserved across SARS and bat coronaviruses remain conserved in the SARS-Cov-2 strains, most of which emerged after our analysis above (Fig. 1A) . We determined the conservation of conserved genome regions from SARSr-MSA-1 across SARS-CoV-2 sequences as of deposition date 03- [18] [19] [20] . For this analysis, we obtained two wholegenome multiple sequence alignments, keeping only full-length genome sequences of at least 29,000 nucleotides in both cases: the first includes 103 NCBI sequences (SARS-CoV-2-MSA-1), and the second includes 739 sequences deposited to GISAID 17 (SARS-CoV-2-MSA-2). We noted conserved regions in the betacoronavirus alignment SARSr-MSA-1 were more likely to be at least 99% conserved in both SARS-CoV-2-MSA-1 and SARS-CoV-2-MSA-2 than random intervals of the same size (binomial test p-value < 1e-5). Table 1 lists these regions, which we term the SARSrelated-conserved regions. These genome regions are conserved across the betacoronavirus sequences in SARSr-MSA-1 and have at least 99% sequence conservation across whole-genome sequences from the SARS-CoV-2 outbreak as of March 18, 2020 (SARS-CoV-2-MSA-2).