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Evolutionary Conservation of Human DNA Methyltransferase 3 Alpha (Dnmt3a) Gene in Acute Myeloid Leukemia (Aml): A Computational Study

Francis Ojochogwu Omale,, Ala Adeola Adefoluke, Michael Izuchukwu Onyejanochie, Corresponding author

Abstract

Acute myeloid leukaemia is an aggressive haematological malignancy characterized by the abnormal proliferation of myeloid precursor cells and disrupted haematopoiesis. The DNA methyltransferase 3 alpha (DNMT3A) gene is a key epigenetic regulator involved in DNA methylation and hematopoietic differentiation, and its mutations are among the most common genetic alterations observed in AML. This study investigated the evolutionary conservation and genetic variation of the human DNMT3A gene using computational and phylogenetic approaches. Ten DNMT3A-related nucleotide sequences were retrieved from the National Center for Biotechnology Information database and analyzed for sequence characteristics, including length and GC content. Multiple sequence alignment was performed using the MUSCLE algorithm in Geneious Prime v9.0.5 to identify conserved and variable regions. Phylogenetic analysis was conducted using the Neighbor-Joining method based on the Tamura–Nei model, while distance matrix analysis was used to evaluate genetic similarity and divergence among the sequences. The results revealed considerable variation in sequence length and GC content among the retrieved sequences. High sequence conservation was observed among several transcript variants, with the highest percentage identities recorded between NM_022552.5 and NM_175629.2 (98.916%), NM_001375819.1 and NM_153759.3 (98.080%), and NM_001320892.2 and NM_175630.1 (96.688%). Phylogenetic analysis grouped the sequences into six clusters and three individual branches, indicating varying levels of evolutionary divergence. Overall, while the retrieved DNMT3A transcript variants showed variation in length and GC content, the coding regions were highly conserved, suggesting strong evolutionary pressure and indicating that mutations in these conserved sites implicated in AML Pathogenesis may serve as targets for future molecular investigations. P-ISSN 2695-222X

Keywords

Acute myeloid leukemiaDNMT3Aevolutionary conservationphylogenetic analysisbioinformaticsDNA methylation.

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