Continuous evolution of user-defined genes at 1 million times the genomic mutation rate

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-11-08 DOI:10.1126/science.adm9073

Gordon Rix, Rory L. Williams, Vincent J. Hu, Aviv Spinner, Alexander (Olek) Pisera, Debora S. Marks, Chang C. Liu

引用次数: 0

Abstract

When nature evolves a gene over eons at scale, it produces a diversity of homologous sequences with patterns of conservation and change that contain rich structural, functional, and historical information about the gene. However, natural gene diversity accumulates slowly and likely excludes large regions of functional sequence space, limiting the information that is encoded and extractable. We introduce upgraded orthogonal DNA replication (OrthoRep) systems that radically accelerate the evolution of chosen genes under selection in yeast. When applied to a maladapted biosynthetic enzyme, we obtained collections of extensively diverged sequences with patterns that revealed structural and environmental constraints shaping the enzyme’s activity. Our upgraded OrthoRep systems should support the discovery of factors influencing gene evolution, uncover previously unknown regions of fitness landscapes, and find broad applications in biomolecular engineering.

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用户定义的基因以 100 万倍于基因组突变率的速度持续进化

当自然界对一个基因进行长时期的大规模进化时，会产生具有保存和变化模式的同源序列多样性，其中包含有关该基因的丰富结构、功能和历史信息。然而，自然基因多样性积累缓慢，很可能排除了功能序列空间的大片区域，从而限制了编码和提取的信息。我们介绍了升级的正交 DNA 复制（OrthoRep）系统，它能从根本上加速酵母中选择基因的进化。当应用于一种适应不良的生物合成酶时，我们获得了广泛分歧的序列集合，其模式揭示了影响酶活性的结构和环境制约因素。我们升级的 OrthoRep 系统将有助于发现影响基因进化的因素，揭示先前未知的适应性景观区域，并在生物分子工程中找到广泛的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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