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Science 328 (5976): 368-372

Copyright © 2010 by the American Association for the Advancement of Science

Rapid Diversification of Cell Signaling Phenotypes by Modular Domain Recombination

Sergio G. Peisajovich,1,* Joan E. Garbarino,1,2 Ping Wei,1,3 Wendell A. Lim1,2,{dagger}

Abstract: Cell signaling proteins are often modular, containing distinct catalytic and regulatory domains. Recombination of such biological modules has been proposed to be a major source of evolutionary innovation. We systematically analyzed the phenotypic diversity of a signaling response that results from domain recombination by using 11 proteins in the yeast mating pathway to construct a library of 66 chimeric domain recombinants. Domain recombination resulted in greater diversity in pathway response dynamics than did duplication of genes, of single domains, or of two unlinked domains. Domain recombination also led to changes in mating phenotype, including recombinants with increased mating efficiency over the wild type. Thus, novel linkages between preexisting domains may have a major role in the evolution of protein networks and novel phenotypic behaviors.

1 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
2 Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.
3 Center for Theoretical Biology, Peking University, Beijing 100871, China.

* Present address: Illumina, Inc., San Diego, CA 92121, USA.

{dagger} To whom correspondence should be addressed. E-mail: lim{at}

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