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.

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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