在DNA复制过程中模板切换是适应性基因放大的主要来源
Julie N Chuong1, Nadav Ben Nun2,3, Ina Suresh1
1Department of Biology, Center for Genomics and Systems Biology, New York University, New York, United States.
eLife
|February 3, 2025
概括
副本数变异 (CNVs) 通过改变基因副本来驱动适应. 基因组架构,包括复制的起源和LTRs,影响CNV的形成和进化,DNA复制模板切换是关键机制.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 副本数变异 (CNVs) 对遗传变异,适应和基因组进化至关重要.
- 基因组架构对CNV形成和动态的影响在很大程度上仍未被探索.
- 众所周知,Saccharomyces cerevisiae中的GAP1基因在氨酸限制下经常经历放大.
研究的目的:
- 研究特定基因组元素 (LTR,ARS) 在 CNV 形成和适应性进化中的作用.
- 量化这些因素对CNV形成率和健康效应的影响.
- 阐明CNV生成的基础机制,包括模板切换和同源重组.
主要方法:
- 缺乏LTRs,ARS或两者的工程酵母菌株在氨酸有限的化学定位器中进化.
- 一个CNV报告员系统被用来监控CNV动态.
- 基于神经网络模拟的推断 (nnSBI) 用于量化 CNV 形成率和健身效应.
主要成果:
- 移除局部DNA元素显著改变了GAP1 CNVs的适应性影响和适应率.
- 由模板切换驱动的来源依赖反向重复放大 (ODIRA) 介导了跨菌株GAP1CNV的26-80%.
- 远端ARS元素和在逆转移子事件后同源重组被确定为替代的CNV调解机制.
结论:
- 基因组架构在塑造CNV介导的适应性进化中发挥着关键作用.
- 在DNA复制过程中模板切换是适应性CNV的重要来源.
- 了解DNA复制,重组和基因组结构之间的相互作用是破译CNV动态的关键.
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