Systematic molecular evolution enables robust biomolecule discovery
Systematic molecular evolution enables robust biomolecule discovery
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DOI：
10.1038/s41592-021-01348-4
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发表时间：
2021-12-30
期刊：
影响因子：
48
通讯作者：
Esvelt, Kevin M.
中科院分区：
文献类型：
--
作者：
DeBenedictis, Erika A.;Chory, Emma J.;Esvelt, Kevin M.
当来自环境的选择压力随着时间的推移形成遗传变异时，进化就发生了。在实验室里，进化通常用于设计蛋白质和RNA，但实验限制了可重复和可靠地探索诸如人口多样性、环境变化的时间和结果的机会等因素的能力。我们开发了一种称为噬菌体和机器人辅助近连续进化（PRANCE）的机器人系统，通过高通量进行噬菌体辅助连续进化，全面探索生物分子进化。PRANCE实现了一个自动反馈控制系统，根据每个分子活性的实时测量来调整选择的严格程度。在进化三种不同类型的生物分子的过程中，我们发现进化是可复制的，既受随机机会的影响，也受环境变化的历史模式的影响。这项工作提高了蛋白质工程的可靠性，使系统分析控制生物分子进化的历史、环境和随机因素成为可能。噬菌体和机器人辅助的近连续进化使噬菌体辅助的高通量连续进化成为可能，从而改进了对序列空间的探索，并深入了解变量如何影响进化结果。
Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited the ability to reproducibly and reliably explore factors such as population diversity, the timing of environmental changes and chance on outcomes. We developed a robotic system termed phage- and robotics-assisted near-continuous evolution (PRANCE) to comprehensively explore biomolecular evolution by performing phage-assisted continuous evolution in high-throughput. PRANCE implements an automated feedback control system that adjusts the stringency of selection in response to real-time measurements of each molecular activity. In evolving three distinct types of biomolecule, we find that evolution is reproducibly altered by both random chance and the historical pattern of environmental changes. This work improves the reliability of protein engineering and enables the systematic analysis of the historical, environmental and random factors governing biomolecular evolution.Phage and robotics-assisted near-continuous evolution enables phage-assisted continuous evolution in high throughput, allowing for improved exploration of sequence space and insight into how variables affect evolution outcomes.