| Autor: |
Panova VV; Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119234, Russia., Dolinnaya NG; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Novoselov KA; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Savitskaya VY; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Chernykh IS; Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119234, Russia., Kubareva EA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia., Alexeevski AV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia.; Department of Mathematics, Scientific Research Institute for System Studies, Russian Academy of Sciences, Nakhimovskii Prospekt 36-1, Moscow 117218, Russia., Zvereva MI; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia. |
| Abstrakt: |
Somatic mutations in the promoter region of the human telomerase reverse transcriptase ( hTERT ) gene have been identified in many types of cancer. The hTERT promoter is known to be enriched with sequences that enable the formation of G-quadruplex (G4) structures, whose presence is associated with elevated mutagenicity and genome instability. Here, we used a bioinformatics tool (QGRS mapper) to search for G4-forming sequences (G4 motifs) in the 1000 bp TERT promoter regions of 141 mammalian species belonging to 20 orders, 5 of which, including primates and predators, contain more than 10 species. Groups of conserved G4 motifs and single-nucleotide variants within these groups were discovered using a block alignment approach (based on the Nucleotide PanGenome explorer). It has been shown that: (i) G4 motifs are predominantly located in the region proximal to the transcription start site (up to 400 bp) and are over-represented on the non-coding strand of the TERT promoters, (ii) 11 to 22% of the G4 motifs found are evolutionarily conserved across the related organisms, and (iii) a statistically significant higher frequency of nucleotide substitutions in the conserved G4 motifs compared to the surrounding regions was confirmed only for the order Primates . These data support the assumption that G4s can interfere with the DNA repair process and affect the evolutionary adaptation of organisms and species. |
