Computational analysis on the dissemination of non-B DNA structural motifs in promoter regions of 1180 cellular genomes.

The promoter regions of gene regulation are under evolutionary constraints and earlier studies uncovered that they are characterized by enrichment of functional non-B DNA structural signatures like curved DNA, cruciform DNA, G-quadruplex, triple-helical DNA, slipped DNA structures, and Z-DNA. However, these studies are restricted to a few model organisms, single non-B DNA motif types, or whole genomic sequences, and their comparative accumulation in promoter regions of different domains of life has not been reported comprehensively. In this study, for the first time, we investigated the preponderance of non-B DNA-prone motifs in promoter regions in 1180 genomes belonging to 28 taxonomic groups using the non-B DNA Motif Search Tool (nBMST). The trends suggest that they are predominant in promoters compared to the upstream and downstream regions of all three domains of life and variably linked to taxonomic groups. Cruciform DNA motif is the most abundant form of non-B DNA, spanning from archaea to lower eukaryotes. Curved DNA motifs are prominent in host-associated bacteria, and suppressed in mammals. Triplex-DNA and slipped DNA structure repeats are discretely dispersed in all lineages. G-quadruplex motifs are significantly enriched in mammals. We also observed that the unique enrichment of non-B DNA in promoters is strongly linked to genome GC, size, evolutionary time divergence, and ecological adaptations. Overall, our work systematically reports the unique non-B DNA structural landscape of cellular organisms from the perspective of the cis-regulatory code of genomes.