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which continues to be neglected by many wildlife and fishery agencies today. This paper may help to rectify that situation by bringing to broader attention the important contrasts between standard hunting and fishing practices (unnatural selection) on the one hand and standard agricultural and aquacultural practices (artificial selection) on the other.

Artificial selection traditionally refers to human-mediated differential propagation of plants or animals with desirable hereditary traits. In the modern biotechnology era, an entirely different form of genetic engineering is possible in which particular proteins are subjected to repeated rounds of mutation and selection, in laboratory test tubes, for improved stability or biochemical function. In Chapter 8, Jesse Bloom and Frances Arnold review this form of directed evolution, which is becoming a powerful approach to the design of new proteins for medicine and pharmacology. Directed protein evolution has also yielded new insights into the fundamental nature of evolutionary processes. The authors emphasize three major conclusions from directed evolution experiments: (i) most desirable protein properties can be incrementally improved through successions of single mutation steps; (ii) much of the epistatic coupling between mutations is due to protein stability and its influence on mutational robustness and protein evolvability; and (iii) adaptive protein evolution is heavily reliant on the prevalence of promiscuous protein functions (initial traces of activity that proteins routinely display on foreign substrates) that in turn are routinely influenced by neutral mutations. Directed protein evolution goes far beyond the wildest imaginings of Darwin, who would doubtless be impressed that the general principles of selection he illuminated would prove to be so universal.



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