Conserved G-Quadruplex-Forming Sequences in Mammalian TERT Promoters and Their Effect on Mutation Frequency

Somatic mutations in the promoter region of human telomerase reverse transcriptase (hTERT) gene have been identified many types cancer. The hTERT is known to be enriched with sequences that enable formation G-quadruplex (G4) structures, whose presence associated elevated mutagenicity and genome instability. Here, we used a bioinformatics tool (QGRS mapper) search for G4-forming (G4 motifs) 1000 bp TERT regions 141 mammalian species belonging 20 orders, 5 which, including primates predators, contain more than 10 species. Groups conserved G4 motifs single-nucleotide variants within these groups were discovered using block alignment approach (based on Nucleotide PanGenome explorer). It has shown that: (i) are predominantly located proximal transcription start site (up 400 bp) over-represented non-coding strand promoters, (ii) 11 22% found evolutionarily across related organisms, (iii) statistically significant higher frequency nucleotide substitutions compared surrounding was confirmed only order Primates. These data support assumption G4s can interfere DNA repair process affect evolutionary adaptation organisms