奥尔杜瓦伊域表达降低了线粒体通路的调节:对人类大脑进化和新陈代谢的影响
Jonathon G Keeney1, David Astling1, Vanessa Andries2,3
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
bioRxiv : the preprint server for biology
|November 1, 2024
概括
与大脑大小相关的Olduvai域减少了线粒体的能量生产. 这种剂量依赖的效果可能会扩大神经生成窗口,使人类和灵长类动物的大脑更大.
科学领域:
- 进化生物学是进化的生物学.
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
背景情况:
- 由NBPF基因家族编码的Olduvai (DUF1220) 蛋白质域显示出显著的人类血统特异性的拷贝数扩张.
- 较高的Olduvai副本数与灵长类动物和人类的大脑大小和神经元数量的增加相关,包括微头症和大头症的变异.
研究的目的:
- 阐明Olduvai域影响神经干细胞增殖和大脑发育的机制.
- 研究NBPF1基因过度表达的功能影响,该基因编码多个Olduvai域.
主要方法:
- 对过度表达NBPF1的细胞进行了转录组 (RNAseq) 和蛋白质组 (质谱) 分析.
- 用基因本体学 (GO) 丰富分析来识别受NBPF1过度表达影响的生物过程和分子功能.
- 使用活细胞成像来验证线粒体外观的变化.
主要成果:
- 无论是RNAseq还是质谱,都表明NBPF1过度表达细胞中的线粒体下调.
- GO分析显示,在下调调节的蛋白质中,线粒体电子运输链显著丰富,NADH脱酶活性被确定为关键的放松调节功能.
- 活细胞成像证实了明显线粒体的减少.
结论:
- 奥尔杜瓦伊域通过线粒体下调调节来调节细胞能量的剂量依赖性减少.
- 这种能量减少可能导致发育减缓,扩大神经生成窗口,促进神经元产生增加和大脑大小增加.
- 拟议的机制也可以解释其他发育过程中的neotenic特征.
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