title: Bioinformatic analysis reveals an evolutional selection for DNA:RNA hybrid G-quadruplex structures as putative transcription regulatory elements in warm-blooded animals.
abstract: Recently, we reported the co-transcriptional formation of DNA:RNA hybrid G-quadruplex (HQ) structure by the non-template DNA strand and nascent RNA transcript, which in turn modulates transcription under both in vitro and in vivo conditions. Here we present bioinformatic analysis on putative HQ-forming sequences (PHQS) in the genomes of eukaryotic organisms. Starting from amphibian, PHQS motifs are concentrated in the immediate 1000-nt region downstream of transcription start sites, implying their potential role in transcription regulation. Moreover, their occurrence shows a strong bias toward the non-template versus the template strand. PHQS has become constitutional in genes in warm-blooded animals, and the magnitude of the strand bias correlates with the ability of PHQS to form HQ, suggesting a selection based on HQ formation. This strand bias is reversed in lower species, implying that the selection of PHQS/HQ depended on the living temperature of the organisms. In comparison with the putative intramolecular G-quadruplex-forming sequences (PQS), PHQS motifs are far more prevalent and abundant in the transcribed regions, making them the dominant candidates in the formation of G-quadruplexes in transcription. Collectively, these results suggest that the HQ structures are evolutionally selected to function in transcription and other transcription-mediated processes that involve guanine-rich non-template strand.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xiao
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zheng
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
mesh_terms: D000818:Animals; D019295:Computational Biology; D004247:DNA / Q000737:chemistry*; D019143:Evolution, Molecular; D054856:G-Quadruplexes; D012313:RNA / Q000737:chemistry*; D050436:Regulatory Elements, Transcriptional; D012641:Selection, Genetic; D024363:Transcription Initiation Site
chemical_list: D012313:RNA; D004247:DNA