Bioinformatic analysis reveals an evolutional selection for DNA:RNA hybrid G-quadruplex structures as putative transcription regulatory elements in warm-blooded animals

• Published in: Nucleic acids research Vol. 41; no. 22; pp. 10379 - 10390
• Main Authors: Xiao, Shan, Zhang, Jia-Yu, Zheng, Ke-Wei, Hao, Yu-Hua, Tan, Zheng
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2013
• Subjects: Animals; Computational Biology; DNA - chemistry; Evolution, Molecular; G-Quadruplexes; Genomics; Regulatory Elements, Transcriptional; RNA - chemistry; Selection, Genetic; Transcription Initiation Site
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkt781

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.