Characterization of MTNR1A Genetic Variations in Nannospalax Rodents

Öz

Members of the genus Nannospalax, commonly known as blind mole rats, are subterranean rodents adapted to low-oxygen environments. These rodents are characterized by their extraordinarily long lifespans and resistance to both spontaneous and induced tumor formation. Although the cause of their cancer resistance is unknown, it is hypothesized that, over centuries of living in their underground niche, these rodents may have developed a cancer resistance mechanism related to circadian rhythms or genes involved in these pathways. This study aims to identify variations in the MTNR1A gene, which is involved in circadian rhythm and melatonin pathway in blind mole rats, and to compare the detected variations with sequences from other species (Homo sapiens, Mus musculus, Heterocephalus glaber, Rattus norvegicus) in databases. For this purpose, PCR analysis of DNA samples obtained from tissues of 18 specimens representing nine different cytotypes belonging four Nannospalax species distributed in Turkey (Nannospalax xanthodon, Nannospalax ehrenbergi, Nannospalax leucodon, and Nannospalax tuncelicus) was performed and these products were sequenced. The relevant DNA base differences were identified by comparing the sequencing results with the reference genome (Nannospalax galili). The detected base differences were compared with the amino acid sequences of the reference and other species to identify existing or potential variations. Accrodingly, only one of the single nucleotide changes in the DNA sequences resulted in an amino acid sequence change. It was concluded that the variation p.N10Q (p.Asp10Glu), corresponding to the 10th amino acid in humans, has been evaluated in the Polyphen-2 database, yielding a score of approximately 0.5, suggesting that this change may have potentially harmful/pathogenic effects.

Anahtar Kelimeler

• Nannospalax
• MTNR1A
• variation
• melatonin
• blind mole rats

Nannospalax Kemirgenlerinde MTNR1A Genetik Varyasyonlarının Karakterizasyonu

Öz

Nannospalax cinsi üyesi körfareler toprakaltı ekolojik nişinde yaşamını sürdüren, düşük oksijenli ortama uyum sağlamış kemirgenlerdir. Olağanüstü uzun ömürleri ve hem spontan hem de indüklenmiş tümör oluşumuna karşı dirençleri ile karakterize edilen kemirgenlerdir. Bu kemirgenlerin kansere olan direncinin sebebi bilinmemekle beraber, yüzyıllardır yaşadıkları toprak altı nişinde sirkadiyen ritim veya bu yolakta görev alan genlerle ilişkili olacak şekilde bir kanser mekanizması geliştirebildikleri varsayılmaktadır. Bu çalışmada körfarelerde sirkadiyen ritimde ve melatonin yolağında görev alan MTNR1A genindeki varyasyonların varlığı ve tespit edilen varyasyonların veritabanındaki diğer türlere (Homo sapiens, Mus musculus, Heterocephalus glaber, Rattus norvegicus) ait dizilerle karşılaştırılması amaçlanmıştır. Bu amaçla, Türkiye’de dağılım gösteren dört Nannospalax türüne ait (Nannospalax xanthodon, Nannospalax ehrenbergi, Nannospalax leucodon ve Nannospalax tuncelicus) 9 farklı sitotip içeren toplam 18 adet örneğe ait dokulardan elde edilen DNA örneklerinin PCR analizi gerçekleştirilerek bu ürünler sekanslanmıştır. Sekans sonuçları ile referans genom (Nannospalax galili) karşılaştırılarak ilgili DNA baz farklılıkları tespit edilmiştir. Tespit edilen baz farklılıkları referans dizi ve diğer türlere ait amino asit dizileri ile karşılaştırılarak var olan/olması muhtemel varyasyonlar belirlenmiştir. Buna göre DNA dizilerindeki tek nükleotid değişimlerinden yalnızca biri amino asit dizisinde değişikliğe sebep olmuş; insanda 10. amino asite denk gelen p.N10Q (p.Asp10Glu) varyasyonu, Polyphen-2 veritabanında yaklaşık 0.5 skoru ile değerlendirilmiş ve mevcut değişimin muhtemel zararlı/patojenik etkileri olabileceği sonucuna varılmıştır.

Anahtar Kelimeler

• Nannospalax
• MTRN1A
• varyasyon
• körfare
• melatonin

Kaynakça

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