从鱼类到Homo sapiens的真核细胞线性图案的进化,这些图案控制了雌激素受体的功能
Antonella Falconieri1,2, Giulia Boarolo1,2, Chiara Boschelle1,2
1Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
Nucleic acids research
|July 19, 2025
概括
这项研究追踪了从鱼类到人类的雄激素受体 (AR) 基因和转化后修饰 (PTM) 的演变. 它揭示了对基因调节和跨物种激素结合至关重要的保存的功能元素.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 了解转录因子 (TF) 的演变对于基因调节至关重要.
- 雄激素受体 (AR) 是一种关键的联体激活TF,参与各种生物过程.
研究的目的:
- 在AR中研究异构的真核细胞线性基因 (ELM),同重复基因 (HReps) 和经过翻译后修改 (PTMs) 的氨基酸的进化史.
- 在脊椎动物物种中识别AR中的保存和新出现的功能元素.
主要方法:
- 在模型 (SWISS-模型,Alphafold3) 的建模.
- 计算的分子动力学模拟.
- 生物化学和分子分析.
主要成果:
- 在人类AR中确定了功能性活跃的ELM,其中一些可追溯到软骨鱼类,其中包括一种对雄性素结合至关重要的联体结合域 (LBD).
- 发现了一种古老的抑制信号,一种通过酸化部位通过PTM调节的ELM,从鱼类保存到人类.
- 在其他类固醇受体及其祖先的LBD中发现了类似的酸化位点.
结论:
- 特定的ELM和PTM早期建立,并在类固醇激素受体 (SHR) 家族中持续存在.
- 突出了从鱼类到人类保存的早期AR特异性ELM,以及后来出现的哺乳动物ELM.
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