Parveen Shakeela, Khan Muhammad Farhan, Sultana Mehwish, Rehman Saif Ur, Shafique Laiba
Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Beibu Gulf University, Guangxi, 535011, People's Republic of China.
Department of Zoology, Government Sadiq College Women University, Bahawalpur, Punjab, Pakistan.
J Appl Genet. 2025 May;66(2):409-420. doi: 10.1007/s13353-024-00924-6. Epub 2024 Nov 28.
Doublesex and Mab-3 (DMRT) gene family is a diverse group of transcriptional factors crucially involved in sex differentiation and biological processes such as body growth and differentiation in vertebrates. In this study, we analyzed DMRT genes structural characterization and physiochemical properties, and elucidated their functional role as a ligand of different gonadal receptors including androgen (AR), estrogen β (ER-β), estrogen γ (ER-γ), and progesterone (PR). All six genes of the DMRT gene family in grass carp (Ctenopharyngodon Idella Valenciennes, 1844) exhibited an acidic nature. These DMRT genes are primarily localized in the nucleus, where they play a role in DNA binding via doublesex DNA binding motif. All the DMRT gene pairs are under strong purifying selection with two segmental duplications envisaged about 18.30 (DMRT3a/DMRTA2) and 24.90 (DMRT2b/DMRT2a) million years ago (MYA). Recombination analysis revealed six potential recombinant breakpoints posing substantial evolutionary pressure for diverse cellular functioning of DMRT isoforms. Moreover, the DMRTA1 protein had a highest binding affinity of - 270.42 and - 267.16 for androgen receptors (AR) and progesterone receptors (PR), whereas, for estrogen receptors ER-β and ER-γ, the maximum binding affinity was observed with DMRT2a and DMRT2b proteins showing a docking score of - 254.22 and - 261.71, respectively. First time we studied the binding scores and interface residues of the DMRT genes as a ligand of gonadal receptors that play a crucial role in fish growth, sex development and differentiation, and spermatogenesis and oocyte maturation. The present study provides a molecular basis for DMRT genes in grass carp that may serve as a reference for in-depth phylogenomic study in other species.
双性和Mab-3(DMRT)基因家族是一组多样的转录因子,在脊椎动物的性别分化以及身体生长和分化等生物学过程中起着至关重要的作用。在本研究中,我们分析了DMRT基因的结构特征和理化性质,并阐明了它们作为不同性腺受体(包括雄激素受体(AR)、雌激素β(ER-β)、雌激素γ(ER-γ)和孕激素受体(PR))配体的功能作用。草鱼(Ctenopharyngodon Idella Valenciennes,1844)的DMRT基因家族的所有六个基因均表现出酸性性质。这些DMRT基因主要定位于细胞核中,在那里它们通过双性DNA结合基序发挥DNA结合作用。所有的DMRT基因对都受到强烈的纯化选择,大约在1830万年前(DMRT3a/DMRTA2)和2490万年前(DMRT2b/DMRT2a)设想有两次片段重复。重组分析揭示了六个潜在的重组断点,对DMRT异构体的多种细胞功能构成了巨大的进化压力。此外,DMRTA1蛋白对雄激素受体(AR)和孕激素受体(PR)的结合亲和力最高,分别为-270.42和-267.16,而对于雌激素受体ER-β和ER-γ,观察到DMRT2a和DMRT2b蛋白的最大结合亲和力,对接分数分别为-254.22和-261.71。我们首次研究了DMRT基因作为性腺受体配体的结合分数和界面残基,这些受体在鱼类生长、性别发育和分化以及精子发生和卵母细胞成熟中起着至关重要的作用。本研究为草鱼的DMRT基因提供了分子基础,可为其他物种的深入系统基因组学研究提供参考。