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environments and challenges. Modularity appears to be a useful feature of evolvable, rapidly-adapting systems—some biological systems and even components are highly modular, such that components and sub-components can be rapidly swapped in and out to generate new functions. Eukaryotic signaling systems are a good example, but prokaryotes rely on much less modular systems that nonetheless serve them very well. Are there costs of evolvability in terms of system performance?

Key Questions

  • When and how can evolutionary methods contribute to design of synthetic systems?

  • How can evolutionary methods be best integrated with “rational” design, including computational design? What is the role of modeling?

  • Are there design objectives that can be addressed only through evolutionary strategies? Are there objectives for which evolutionary strategies are unnecessary?

  • What are the best targets for evolutionary optimization? Molecules? Circuits? Organisms?

  • What technologies and tools will be needed for rapid, efficient evolutionary optimization?

  • What strategies can we use to overcome the tendency of synthetic biological systems to mutate and escape programmed control?

  • How do we design systems and host organisms to ensure genetic stability?

  • How can we best understand mechanisms and consequences of mutation and develop routes for repair that enable designed functionality to be maintained?

  • To what extent is it important to pursue strategies for designing evolvable systems? What are the key features?


Haseltine EL, Arnold FH. Synthetic gene circuits: design with directed evolution. Annu Rev Biophys Biomol Struct 2007;36:1-19:;searchHistoryKey=%24%7BsearchHistoryKey%7D. Accessed online 28 July 2009.

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