Genome-wide regulatory dynamics of G-quadruplexes in human malaria parasite Plasmodium falciparum

The AT-rich genome of P. falciparum has uniquely localized G-rich stretches that have propensity to form G-quadruplexes. However, their global occurrence and potential biological roles in the parasite are poorly explored. Our genome-wide analysis revealed unique enrichment of quadruplexes in P. falciparum genome which was remarkably different from other Plasmodium species. A distinct predominance of quadruplexes was observed in nuclear and organellar genes that participate in antigenic variation, pathogenesis, DNA/RNA regulation, metabolic and protein quality control processes. Data also suggested association of quadruplexes with SNPs and DNA methylation. Furthermore, analysis of steady state mRNA (RNA-seq) and polysome-associated mRNA (Ribosome profiling) data revealed stage-specific differences in translational efficiency of quadruplex harboring genes. Taken together, our findings hint towards existence of regulatory dynamics associated with quadruplexes that may modulate translational efficiency of quadruplex harboring genes to provide survival advantage to the parasite against host immune response and antimalarial drug pressure.