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通过定向进化探索蛋白质适应度景观。

Exploring protein fitness landscapes by directed evolution.

作者信息

Romero Philip A, Arnold Frances H

机构信息

Division of Chemistry and Chemical Engineering, 21041, California Institute of Technology, Pasadena, California 91125, USA.

出版信息

Nat Rev Mol Cell Biol. 2009 Dec;10(12):866-76. doi: 10.1038/nrm2805.

Abstract

Directed evolution circumvents our profound ignorance of how a protein's sequence encodes its function by using iterative rounds of random mutation and artificial selection to discover new and useful proteins. Proteins can be tuned to adapt to new functions or environments by simple adaptive walks involving small numbers of mutations. Directed evolution studies have shown how rapidly some proteins can evolve under strong selection pressures and, because the entire 'fossil record' of evolutionary intermediates is available for detailed study, they have provided new insight into the relationship between sequence and function. Directed evolution has also shown how mutations that are functionally neutral can set the stage for further adaptation.

摘要

定向进化通过随机突变和人工选择的迭代轮次来发现新的有用蛋白质,从而规避了我们对蛋白质序列如何编码其功能的极度无知。通过涉及少量突变的简单适应性进化过程,蛋白质可以被调整以适应新功能或新环境。定向进化研究表明,在强大的选择压力下,一些蛋白质能够多么迅速地进化,而且由于进化中间体的完整“化石记录”可供详细研究,这些研究为序列与功能之间的关系提供了新的见解。定向进化还表明,功能中性的突变如何能够为进一步的适应性变化奠定基础。

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