pam med j Pamukkale Medical Journal 1308-0865 Pamukkale University 10.31362/patd.1659805 Clinical Sciences (Other) Klinik Tıp Bilimleri (Diğer) Ancient DNA and MTHFR mutation: insights into human evolution and health Antik DNA ve MTHFR mutasyonu: insan sağlığına ilişkin bulgular https://orcid.org/0000-0003-4832-0436 Koseler Aylin PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ https://orcid.org/0000-0002-0171-318X Söğüt Bilal PAMUKKALE ÜNİVERSİTESİ 04 13 2026 19 2 231 236 03 18 2025 05 07 2025 Copyright © 2008, Pamukkale Medical Journal 2008 Pamukkale Medical Journal

Purpose: Scientists have discovered more information on ancient genes, migration patterns, and human population evolution by studying DNA extracted from old samples. This research aimed to synthesize current understanding of the relationship between MTHFR mutation and ancient DNA, exploring possible implications for our understanding of the evolutionary and genetic underpinnings of disorders.Materials and methods: Genomic DNA isolation from petrous bone and teeth samples was performed using the Ancient DNA extraction from bones and teeth kit. In the obtained genomic DNAs, the gene-specific region was amplified by PCR, and the polymorphic locus located in this region was observed on high-resolution agarose gel. The MTHFR mutation was examined by genotyping based on DNA sequence analysis.Results: MTHFR A1298C mutation was detected in three samples and MTHFR C1298C mutation was detected in one sample.Conclusion: Looking at MTHFR changes in ancient DNA helps scientists understand how these gene differences affected human survival.

Amaç: Bilim insanları eski örneklerden çıkarılan DNA'yı inceleyerek eski genler, göç kalıpları ve insan popülasyonunun evrimi hakkında daha fazla bilgi keşfettiler. Bu araştırma, MTHFR mutasyonu ile eski DNA arasındaki ilişkiye dair mevcut anlayışı sentezlemeyi ve bozuklukların evrimsel ve genetik temellerine dair anlayışımız için olası çıkarımları keşfetmeyi amaçladı.Gereç ve yöntem: Petroz kemik ve diş örneklerinden genomik DNA izolasyonu, kemik ve dişlerden Antik DNA çıkarma kiti kullanılarak gerçekleştirildi. Elde edilen genomik DNA'larda, gen-spesifik bölge PCR ile çoğaltıldı ve bu bölgede bulunan polimorfik lokus yüksek çözünürlüklü agar jelinde gözlemlendi. MTHFR mutasyonu, DNA dizi analizine dayalı genotipleme ile incelendi.Bulgular: Üç örnekte MTHFR A1298C mutasyonu ve bir örnekte MTHFR C1298C mutasyonu tespit edildi.Sonuç: Eski DNA'daki MTHFR değişikliklerine bakmak, bilim insanlarının bu gen farklılıklarının insanların hayatta kalmasını nasıl etkilediğini anlamalarına yardımcı olur.

 Archaeogenetics MTHFR ancient DNA polymorphism stratonikeia Arkeogenetik MTHFR antik DNA polimorfizm stratonikeia Pääbo S, Gifford JA, Wilson AC. Mitochondrial DNA sequences from a 7000-year old brain. Nucleic Acids Res. 1988;16(20):9775-9787. doi:10.1093/nar/16.20.9775 Cooper A, Poinar HN. Ancient DNA: do it right or not at all. Science. 2000;289(5482):1139. doi:10.1126/science.289.5482.1139b Teixeira, JC. Ancient DNA: a direct window into the human past. Antropologia Portuguesa. 2024;(41):297-312. doi:10.14195/2182-7982_41_17 Ronaghi M, Karamohamed S, Pettersson B, Uhlén M, Nyrén P. Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem. 1996;242(1):84-89. doi:10.1006/abio.1996.0432 Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem. 2009;55(4):641-658. doi:10.1373/clinchem.2008.112789 Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. Neandertal DNA sequences and the origin of modern humans. Cell. 1997;90(1):19-30. doi:10.1016/s0092-8674(00)80310-4 Frieman CJ, Hofmann D. Present pasts in the archaeology of genetics, identity, and migration in Europe: a critical essay. World archaeology. 2019;51(4):528-545. doi:10.1080/00438243.2019.1627907 Söğüt B. Zaman tünelinde gezilen kent: Stratonikeia. Lykos Dergisi. 2014. Robien K, Ulrich CM. 5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol. 2003;157(7):571-582. doi:10.1093/aje/kwg024 Izmirli M. A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk. Mol Biol Rep. 2013;40(1):625-637. doi:10.1007/s11033-012-2101-2 Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10. doi:10.1016/j.ejmg.2014.10.004 Rainero I, Vacca A, Roveta F, Govone F, Gai A, Rubino E. Targeting MTHFR for the treatment of migraines. Expert Opin Ther Targets. 2019;23(1):29-37. doi:10.1080/14728222.2019.1549544 Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995;274(13):1049-1057. doi:10.1001/jama.1995.03530130055028 Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993;39(9):1764-1779. Yi P, Pogribny I, Jill James S. Multiplex PCR for simultaneous detection of 677 C-->T and 1298 A-->C polymorphisms in methylenetetrahydrofolate reductase gene for population studies of cancer risk. Cancer Lett. 2002;181(2):209. doi:10.1016/s0304-3835(02)00060-5 Hofreiter M, Paijmans JL, Goodchild H, et al. The future of ancient DNA: Technical advances and conceptual shifts. Bioessays. 2015;37(3):284-293. doi:10.1002/bies.201400160 Raghubeer S, Matsha TE. Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks. Nutrients. 2021;13(12):4562. Published 2021 Dec 20. doi:10.3390/nu13124562 Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics. 2001;1(3):189-201. doi:10.2165/00129785-200101030-00004 Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132(1):e6-e9. doi:10.1161/CIRCULATIONAHA.114.013311