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We model the process of directed evolution (DE) in silico using genetic algorithms. Making use of the NK fitness landscape model, we analyse the effects of mutation rate, crossover and selection pressure on the performance of DE. A range of values of K, the epistatic interaction of the landscape, are considered, and high- and low-throughput modes of evolution are compared. Our findings suggest that for runs of or around ten generations' duration-as is typical in DE-there is little difference between the way in which DE needs to be configured in the high- and low-throughput regimes, nor across different degrees of landscape epistasis. In all cases, a high selection pressure (but not an extreme one) combined with a moderately high mutation rate works best, while crossover provides some benefit but only on the less rugged landscapes. These genetic algorithms were also compared with a "model-based approach" from the literature, which uses sequential fixing of the problem parameters based on fitting a linear model. Overall, we find that purely evolutionary techniques fare better than do model-based approaches across all but the smoothest landscapes.

Original publication

DOI

10.1016/j.jtbi.2008.11.005

Type

Journal article

Journal

Journal of theoretical biology

Publication Date

03/2009

Volume

257

Pages

131 - 141

Addresses

Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester, M1 7ND, UK. david.wedge@manchester.ac.uk

Keywords

Animals, Proteins, Mutation, Algorithms, Models, Genetic, Research Design, Selection, Genetic, Biological Evolution