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Exploring protein fitness landscapes by directed evolution

2009; Nature Portfolio; Volume: 10; Issue: 12 Linguagem: Inglês

10.1038/nrm2805

1471-0080

Philip A. Romero, Frances H. Arnold,

RNA and protein synthesis mechanisms

Directed evolution optimizes protein function through successive generations of random mutation, artificial selection and screening. This design algorithm provides a reliable approach to engineering proteins with new and useful properties, and helps us to understand how natural evolution occurs. 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 tunedto 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.