线粒体异质体的纵向变化显示了有害变异的积极选择
Lieke M Kuiper1, Wen Shi2, Joost Verlouw1
1Genetic Laboratory, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
medRxiv : the preprint server for health sciences
|April 8, 2024
概括
线粒体DNA (mtDNA) 的体质突变异质体随着年龄的增长而增加. 这项研究表明,有害突变在细胞水平上被积极选择,尽管整体死亡风险增加.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 人类的衰老的特点是体质突变的积累.
- 线粒体易受DNA突变的影响,导致线粒体DNA异质.
- 以前的研究将异质体增加与参与者的年龄和遗传漂移联系起来.
研究的目的:
- 为了研究线粒体DNA的纵向变化.异质.
- 为了确定异质体变异异基因分数 (VAF) 和死亡风险之间的关系.
- 挑战体质mtDNA突变的遗传漂移假设.
主要方法:
- 在两个前性队列 (n=1405) 上进行了一项大型纵向研究.
- 在两个时间点测量了线粒体DNA异质体,平均间隔为8.6年.
- 分析了异质的变异性等位基因分数 (VAF) 的变化.
主要成果:
- 损伤性异质质瘤显示,变异性等位基因分数 (VAF) 增加的可能性更高.
- 增加VAF显著与整体死亡率的风险增加有关.
- 结果表明,在细胞水平上对有害突变的积极选择.
结论:
- 身体线粒体DNA突变不仅仅是由于遗传漂移.
- 积极选择对细胞内预测的有害突变起作用.
- 线粒体DNA异质体积累对衰老和死亡率有影响.
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