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.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
在适应性进化过程中,基因组元素会影响复制数变异 (CNV) 的速率和适应性. 转换DNA复制模板是产生这些自适应CNV的常见机制.
科学领域:
- 进化遗传学的进化遗传学
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 副本数变异 (CNVs) 是适应和基因组进化的关键驱动因素.
- 影响CNV形成,大小,速率和健康效应的因素尚不清楚.
- 假设局部基因组架构会影响CNV动态.
研究的目的:
- 研究局部基因组元素 (LTR,ARS) 在适应性CNVs的形成,适应性和进化动态上的作用.
- 量化工程酵母菌株中CNV形成率和健康效应.
- 阐明 CNV 形成背后的分子机制.
主要方法:
- 在氨酸有限的化疗状态中,Saccharomyces cerevisiae的实验进化.
- 缺乏特定基因组元素 (LTR,ARS) 的工程菌株.
- 使用CNV报告员系统和基于神经网络模拟的推断 (nnSBI) 来量化速度和适应性.
- 基因组序列分析以确定CNV形成机制.
主要成果:
- 适应性*GAP1* CNV 在工程菌株中反复形成并增加频率.
- 移除局部LTR和ARS显著改变了CNV形成率,健康效应和适应率.
- 由模板切换在DNA复制过程中驱动的来源依赖反向重复放大 (ODIRA),介导26-80%的*GAP1*CNVs.
- 远端ARS和同源重组可以在缺乏局部元素的情况下调解CNV形成.
结论:
- 当地基因组架构极大地影响了适应性CNVs的速度和适应性后果.
- 在DNA复制过程中模板切换是适应性CNV的主要来源.
- 酵母基因组在产生适应性遗传变异方面表现出了显著的可塑性.
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