G-quadruplexes may determine the landscape of recombination in HSV-1

BMC Genomics. 2019 May 16;20(1):382. doi: 10.1186/s12864-019-5731-0.


Background: Several lines of evidence suggest that recombination plays a central role in replication and evolution of herpes simplex virus-1 (HSV-1). G-quadruplex (G4)-motifs have been linked to recombination events in human and microbial genomes, but their role in recombination has not been studied in DNA viruses.

Results: The availability of near full-length sequences from 40 HSV-1 recombinant strains with exact position of the recombination breakpoints provided us with a unique opportunity to investigate the role of G4-motifs in recombination among herpes viruses. We mapped the G4-motifs in the parental and all the 40 recombinant strains. Interestingly, the genome-wide distribution of breakpoints closely mirrors the G4 densities in the HSV-1 genome; regions of the genome with higher G4 densities had higher number of recombination breakpoints. Biophysical characterization of oligonucleotides from a subset of predicted G4-motifs confirmed the formation of G-quadruplex structures. Our analysis also reveals that G4-motifs are enriched in regions flanking the recombination breakpoints. Interestingly, about 11% of breakpoints lie within a G4-motif, making these DNA secondary structures hotspots for recombination in the HSV-1 genome. Breakpoints within G4-motifs predominantly lie within G4-clusters rather than individual G4-motifs. Of note, we identified the terminal guanosine of G4-clusters at the boundaries of the UL (unique long) region on either side of the OriL (origin of replication within UL) represented the commonest breakpoint among the HSV-1 recombinants.

Conclusion: Our findings suggest a correlation between the HSV-1 recombination landscape and the distribution of G4-motifs and G4-clusters, with possible implications for the evolution of DNA viruses.

Keywords: G-quadruplexes; G4- clusters; Herpes simplex virus-1; Higher-order G4 s; Recombination breakpoints.

MeSH terms

  • Chromosome Breakpoints*
  • DNA Replication
  • DNA, Viral / genetics*
  • G-Quadruplexes*
  • Genome, Viral*
  • Herpesvirus 1, Human / genetics*
  • Humans
  • Recombination, Genetic*


  • DNA, Viral