Rapid Diversification of Cell Signaling Phenotypes by Modular Domain Recombination

Domain Swaps to Phenotype Shifts For natural selection there must be mechanisms that create phenotypic diversity, presumably from relatively simple molecular changes in an organism. Peisajovich et al. (p. 368) tested the extent to which changes in phenotype can occur by systematic swapping of protein domains in the components of the biochemical signaling pathway that controls mating in yeast. Such changes decreased or increased responsiveness to yeast mating pheromone, and some translated into changes in mating efficiency. The authors propose that shuffling of modular protein domains may be an important source of phenotypic diversity in evolution and may also be a useful strategy for the engineering of biological systems. Systematic swapping of modular protein domains verifies a mechanism for generation of phenotypic diversity in yeast. 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.