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.

中文翻译：

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用户定义的基因以 100 万倍的基因组突变率连续进化


当自然界在亿万年的时间里大规模进化一个基因时，它会产生多种同源序列，这些序列具有守恒和变化的模式，其中包含有关该基因的丰富结构、功能和历史信息。然而，天然基因多样性积累缓慢，并且可能排除了功能序列空间的大区域，从而限制了编码和可提取的信息。我们引入了升级的正交 DNA 复制 （OrthoRep） 系统，该系统从根本上加速了酵母中所选基因的进化。当应用于适应不良的生物合成酶时，我们获得了广泛不同的序列集合，这些序列的模式揭示了塑造酶活性的结构和环境限制。我们升级后的 OrthoRep 系统应该支持发现影响基因进化的因素，揭示以前未知的健身景观区域，并在生物分子工程中找到广泛的应用。