用户定义的基因在100万倍基因组突变率的持续进化
bioRxiv : the preprint server for biology
|November 28, 2023
概括
研究人员将数百万年的基因进化压缩到实验室时间尺度中,使用一种新的正交DNA复制 (OrthoRep) 系统. 这种方法加速了基因适应因子的发现,并揭示了超越自然变异的新进化见解.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 数百万年来的自然基因进化产生了丰富的结构,功能和历史信息的同源序列.
- 然而,自然多样性可能排除功能序列空间,并包含进化异常,限制提取的信息.
研究的目的:
- 开发一种实验方法,将长期的基因进化压缩到实验室时间表中.
- 为了使适应和分歧的直接观察能够推断基因进化上的约束.
主要方法:
- 介绍了一种新的正交DNA复制 (OrthoRep) 系统,用于持久的基因突变.
- 实现突变率超过10^-4的替代基在体内.
- 使用OrthoRep系统开发一种有条件必要的不适应酶.
主要成果:
- 产生了数千个独特的多突变序列,差异>15%.
- 确定了影响酶适应的已知和新型因素.
- 通过在自然变异上训练的机器学习模型证明进化序列适应性是不可预测的.
结论:
- 在OrthoRep系统促进了基因进化约束的前性和系统的发现.
- 能够在健身场景中发现新的区域.
- 在生物分子工程和进化研究中提供了广泛的应用.
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