人类血统突变调节了参与人类进化中的保留基因NTRK2和ITPR1的RNA-蛋白结合
Wenxiang Cai1,2, Weichen Song1,2, Shunying Yu1,2
1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
General psychiatry
|May 21, 2024
概括
一小部分的人类血统突变 (HLMs) 显著影响RNA结合蛋白,影响人类进化和物种化关键的大脑相关基因.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 计算生物学 计算生物学
背景情况:
- 人类血统突变 (HLMs) 通过转录后修饰在塑造人类进化中的确切作用仍然在很大程度上是未知的.
- 了解这些遗传变化对于破译人类特有的特征至关重要.
研究的目的:
- 研究HLMs对人类进化的贡献,特别关注它们对转录后修饰过程的影响.
- 为了确定受HLMs影响的特定基因和通路,这些基因可能推动了人类的物种化.
主要方法:
- 一个深度学习模型Seqweaver被用来预测HLMs对RNA结合蛋白 (RBP) 亲和力的影响.
- 分析的重点是人类常见变异的前1%内的HLM,以确定重大影响.
主要成果:
- 只有0.27%的HLM对RBPs产生了重大影响,这突显了这些突变的选择性作用.
- 受影响的基因在成年刺激性和产前普金耶神经元中得到丰富,这些神经元参与突触组织和GTPase通路.
- 这些基因还含有与神经发育障碍,性衰竭和精神分裂症相关的破坏性突变,NTRK2和ITPR1显示了功能重要性的大量证据.
结论:
- 一个精选的人类特异性突变组可能有助于人类的物种化.
- 这些突变通过对大脑功能和认知进化至关重要的关键基因的转录后修改来发挥影响.
关键词:
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