解读快速进化的保存元素在灵长类大脑发育中的作用,并探索它们在阿尔茨海默病中的潜在参与
Benxia Hu1, Xiao-Lin Zhuang1, Long Zhou2,3
1Key Laboratory of Genetic Evolution & Animal Models, Kunming Natural History Museum of Zoology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Molecular biology and evolution
|January 4, 2024
概括
我们在灵长类动物进化过程中确定了快速演变的保存元素 (RECE),这些元素与大脑扩张和功能有关. 这些元素在阿尔茨海默氏症中表现出改变的活性.
科学领域:
- 进化基因组学是进化的基因组学.
- 神经科学是一个神经科学.
- 灵长类动物的进化
背景情况:
- 人类特有的加速区域是人类大脑进化的关键.
- 祖先灵长类动物中快速演变的保存元素 (RECE) 的特征和功能在很大程度上是未知的.
研究的目的:
- 在灵长类动物进化过程中识别和描述 RECE.
- 研究RECEs的 cis调节功能和大脑表达.
- 探索RECEs在大脑衰老和阿尔茨海默病 (AD) 中的作用.
主要方法:
- 对大型灵长类动物基因组组合的分析.
- 综合性多原子分析 (cis调节功能,基因表达,染色质可访问性).
- 对抗阿兹海默症患者与对照患者的寡基细胞染色质可访问性的比较.
主要成果:
- 在Simiiformes祖先中保存的888个RECE被确定,这是一种加速进化和扩大大脑质量的血统.
- RECE 含有在成年人大脑中活跃的 cis 调节序列.
- 与RECE相关的基因在成人与胎儿大脑中显示出不同的表达模式.
- 从患有阿尔茨海默氏症的个体的寡类细胞中增加了RECE染色质可访问性.
结论:
- RECE是灵长类大脑进化中的重要元素.
- RECEs可能在成人大脑功能,衰老和阿尔茨海默病中发挥作用.
- 这些发现扩大了对灵长类大脑进化的遗传基础的理解.
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