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Characterizing Transcriptional Regulatory Sequences in Coronaviruses and Their Role in Recombination
Yiyan Yang1, Wei Yan1, A Brantley Hall2,3
1National Library of Medicine, National Institutes of Health, Bethesda, MD.
Abstract:
Novel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3,509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently colocated with TRS-B sites than expected.
Insights
Recombination in coronaviruses, like SARS-CoV-2, may occur at transcriptional regulatory sequences (TRS). Our study found that recombination hotspots frequently overlap with TRS-B sites, supporting this hypothesis.
Area of Science:
- Virology
- Genomics
- Molecular Biology
Background:
- Coronaviruses, including SARS-CoV-2, SARS, and MERS, frequently undergo recombination.
- RNA virus recombination is driven by template switching during replication.
- Transcriptional regulatory sequences (TRS) are involved in coronavirus transcription via template switching.
Purpose of the Study:
- To systematically identify transcriptional regulatory sequences (TRS) in coronavirus genomes.
- To investigate the hypothesis that TRS sites are recombination hotspots.
- To analyze the conservation of TRS elements within and between coronavirus genera.
Main Methods:
- Development and application of a tool named SuPER for TRS identification.
- Analysis of 465 coronavirus genomes to identify TRS-L and TRS-B.
- Examination of recombination breakpoint locations relative to TRS-B core sequences.
Main Results:
- Identified 465 TRS-L and 3,509 TRS-B across 506 coronavirus genomes.
- Observed conservation of TRS-L core sequence and leader sequence secondary structure within genera.
- Found a significant co-location of recombination hotspots with TRS-B sites.
Conclusions:
- The study provides evidence supporting the hypothesis that TRS sites are recombination hotspots in coronaviruses.
- TRS elements exhibit conserved features within genera but divergence between genera.
- The findings enhance understanding of coronavirus evolution and recombination mechanisms.
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