Kaplan, Oktay I.Berber, BurakHekim, NezihDoluca, Osman2023-06-162023-06-1620160305-10481362-4962https://doi.org/10.1093/nar/gkw769https://hdl.handle.net/20.500.14365/1843Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development of next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles relies on topological changes such as hairpin formation at the DNA or RNA level. G-quadruplexes, non-canonical nucleic acid topologies with little established biological roles, are increasingly considered for conserved regulatory element discovery. Since the tertiary structure of G-quadruplexes is strongly dependent on the loop sequence which is disregarded by the generally accepted algorithm, we hypothesized that G-quadruplexes with similar topology and, indirectly, similar interaction patterns, can be determined using phylogenetic clustering based on differences in the loop sequences. Phylogenetic analysis of 52 G-quadruplex forming sequences in the Escherichia coli genome revealed two conserved G-quadruplex motifs with a potential regulatory role. Further analysis revealed that both motifs tend to form hairpins and G quadruplexes, as supported by circular dichroism studies. The phylogenetic analysis as described in this work can greatly improve the discovery of functional G-quadruplex structures and may explain unknown regulatory patterns.eninfo:eu-repo/semantics/openAccessEscherichia-ColiDna StructuresRegulatory MotifsBinding-ProteinsPromoter RegionG-QuartetsClustal-WSequenceIdentificationConsequencesArticle10.1093/nar/gkw7692-s2.0-84994634538