title: Rapid diversification of cell signaling phenotypes by modular domain recombination.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Peisajovich
authors.forename: Joan E
authors.initials: JE
authors.lastname: Garbarino
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Lim
mesh_terms: D020134:Catalytic Domain; D020440:Gene Duplication; D005800:Genes, Fungal; D017930:Genes, Reporter; D014644:Genetic Variation; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019151:Peptide Library; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051964:Receptors, Mating Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C048632:MF(ALPHA)1 protein, S cerevisiae; D019151:Peptide Library; D011498:Protein Precursors; D051964:Receptors, Mating Factor; D011993:Recombinant Fusion Proteins; C498031:STE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases
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