选择促进了线粒体基因组的年龄依赖性退化
Ekaterina Korotkevich1, Daniel N Conrad2, Zev J Gartner2
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
bioRxiv : the preprint server for biology
|October 10, 2024
概括
线粒体DNA (mtDNA) 突变因选择而随着年龄的增长而加速,而不仅仅是中性漂移. 赋予生长优势的驱动突变和对功能性等位基因的破坏性选择驱动了肝细胞中的这种积累.
科学领域:
- 遗传学 是一个遗传学.
- 老年学是一门学科.
- 分子生物学分子生物学
背景情况:
- 线粒体DNA (mtDNA) 中的体性突变随着年龄的增长而呈指数级积累.
- 了解驱动这种积累的力量对于衰老研究和疾病至关重要.
- 以前的模型通常假定mtDNA突变的中性积累.
研究的目的:
- 描述老鼠和人类肝脏中年龄积累的mtDNA突变的谱.
- 为了识别加速mtDNA突变积累超出中性预测的选择性力量.
- 了解选择在老化过程中的mtDNA突变动态中的作用.
主要方法:
- 从小鼠和人类肝脏组织的单细胞测序.
- 随着时间的推移对mtDNA突变光谱和等位基因频率的分析.
- 计算建模以区分中性漂移和选择性压力.
主要成果:
- 确定了加速肝细胞中mtDNA突变积累的定向力.
- 赋予复制优势的"驾驶员"突变的数量增加,携带"乘客"突变.
- 观察到"破坏性"选择的证据,有利于缺乏功能的mtDNA等位基因.
结论:
- 选择性力量,包括复制优势和破坏性选择,促进老年肝细胞中mtDNA突变的积累.
- 这些过程有助于mtDNA突变的流行,并可能加速线粒体疾病.
- 选择性积累mtDNA突变影响编码区域,挑战进化保护假设.
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