Investigation of Clock Gene Variations in Nannospalax Cytotypes

İlkay Ci̇velek, T. Kankılıç, D. Akin
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Abstract

Blind mole rats (Nannospalax) are subterranean mammals noted for their longevity and cancerresistance. It is known that these animals' vestigial eyes, particularly the Harder gland around the eyes, maygenerate considerable amounts of melatonin. Furthermore, the melatonin production mechanism in thecircadian rhythm cycle of blind mole rats is regarded to be different from that of other living beings. Themelatonin and Clock genes are hypothesized to be linked to the formation, development, and spread ofcancer, but the researchers still cannot explain their extraordinary cancer resistance.In this study, we hypothesized that the melatonin production mechanism in the circadian rhythm cycle ofblind mole rats, which have been shown in the literature to be cancer-resistant, may differ from that of otherliving species due to the difference in their amino acid variations. Differences in the DNA of the Clockgenes (Cry1 and Per1) involved in melatonin biosynthesis in blind mole rats were studied compared toother model species (Spalax galili, Mus musculus, Heterocephalus glaber, Rattus norvegicus, and Homosapiens). As a result, while no variations were found in the Cry1 gene; only p.G7R variation was found inthe Per1 gene. The SNAP2 software had demonstrated that the human analogs of this variation harmfuleffects. It was suggested that more or full exon sites, more samples and genes should be studied to observemore variants in Nannospalax species. Thereby, the cancer resistance of blind mole rats may be explainedbetter by these variations and the functions of protein domains where these variants are located in.
纳米藻细胞型时钟基因变异的研究
盲鼹鼠(Nannospalax)是一种地下哺乳动物,以长寿和抗癌而闻名。众所周知,这些动物的退化眼睛,特别是眼睛周围的硬腺,可能会产生相当数量的褪黑激素。此外,盲鼹鼠昼夜节律周期中褪黑素的产生机制被认为与其他生物不同。褪黑激素和生物钟基因被认为与癌症的形成、发展和扩散有关,但研究人员仍然无法解释它们非凡的抗癌能力。在这项研究中,我们假设盲鼹鼠的昼夜节律周期中褪黑激素的产生机制可能与其他生物不同,因为它们的氨基酸变异不同。盲鼹鼠在文献中被证明具有抗癌能力。研究了盲鼹鼠体内参与褪黑激素生物合成的时钟基因Cry1和Per1与其他模式物种(Spalax galili、Mus musus、Heterocephalus glaber、Rattus norvegicus和Homosapiens) DNA的差异。结果,在Cry1基因中没有发现变异;在Per1基因中只发现了p.G7R变异。SNAP2软件已经证明,这种变异的人类类似物会产生有害影响。建议对更多或完整的外显子位点、更多的样本和基因进行研究,以观察Nannospalax种的更多变异。因此,这些变异和这些变异所在的蛋白质结构域的功能可以更好地解释盲鼹鼠的抗癌能力。
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