G-quadruplex motifs are functionally conserved in cis-regulatory regions of pathogenic bacteria: An in-silico evaluation.

The role of G-quadruplexes in the cellular physiology of human pathogenesis is an intriguing area of research. Nonetheless, their functional roles and evolutionary conservation have not been compared comprehensively in pathogenic forms of various bacterial genera and species. In the current in silico study, we addressed the role of G-quadruplex-forming sequences (G4 motifs) in the context of cis-regulation, expression variation, regulatory networks, gene orthology and ontology. Genome-wide screening across seven pathogenic genomes using the G4Hunter tool revealed the significant prevalence of G4 motifs in cis-regulatory regions compared to the intragenic regions. Significant conservation of G4 motifs was observed in the regulatory region of 300 orthologous genes. Further analysis of published ChIP-Seq data (Minch et al., 2015) of 91 DNA-binding proteins of the M. tuberculosis genome revealed significant links between G4 motifs and target sites of transcriptional regulators. Interestingly, the transcription factors entangled with virulence, in specific, CsoR, Rv0081, DevR/DosR, and TetR family are found to have G4 motifs in their target regulatory regions. Overall the current study applies positional-functional relationship computation to delve into the cis-regulation of G-quadruplex structures in the context of gene orthology in pathogenic bacteria.