Extended Data Figure 7 |. Interaction between transcription regulatory sequences and RdRp fidelity.

tARC-seq detected chimeric junctions between canonical TRSs in WT SARS-CoV-2 (Fig. 3a). a, However, many of the observed junctions lay outside canonical regions, suggesting non-programmed template switching by a promiscuous polymerase. b, While tARC-seq has the sensitivity to detect single events, the data was filtered further to include only high confidence junctions with ≥100 observations. Even after increasing the stringency to remove potential ligation artifacts (Fig. 1, step 2), many non-canonical junctions remained. Each arc represents a chimeric alignment where the left and right x-intercepts correspond to the 5’ and 3’ junction coordinates and line shading reflects frequency. c-d, While TRS regions comprise only ~3.5% of the SARS-CoV-2 genome, they incur RNA variants at a higher frequency in both WT and Alpha virus. Each TRS region (n=10) is small (<115 nt) and composed of one canonical TRS site plus 100 flanking nucleotides.