Investigation of Clock genes (Bmal1, Per1, Cry1, Cry2 and Per2) gene variants involved in melatonin biosynthesis in Nannospalax (Mammalia: Rodentia) cytotypes

Blind mole rats are known for their long lifespan and resistance to cancer. However, the reason for this cancer resistance is unclear. It is suggested that their different melatonin synthesis mechanism, possibly due to their unique lifestyle, may contribute to their cancer resistance. This PhD thesis investigated genetic variations in Clock genes (Bmal1, Cry1, Cry2, Per1, and Per2), which are essential for melatonin biosynthesis, in Turkish Nannospalax species. These variations were also compared with those in Nannospalax galili, Mus musculus, Heterocephalus glaber, Rattus norvegicus, and Homo sapiens. Furthermore, their potential pathogenic effects in humans were examined through DNA-based screening of specific exon regions. Then, analyses were performed using various bioinformatics tools and databases such as NCBI Blast, Ensembl, Polyphen-2, SNAP2, and String. A total of 29 variations were identified, with 11 in the Per1 gene, 7 in the Per2 gene, 2 in the Cry1 gene, and 9 in the Cry2 geneNo variation was observed in the Bmal1 gene. Some of these detected variations are situated within regions associated with DNA repair processes in response to light-induced UV damage. Additional variations were identified in the PAS domain and 5'-UTR regions, while the rest of the variations were located in non-domain regions of the proteins. Further investigation of clock gene variations may provide important clues on how to identify and prioritize these variations for future studies.