title: Diversifying selection at the Bacillus quorum-sensing locus and determinants of modification specificity during synthesis of the ComX pheromone.
abstract: The competence quorum-sensing system of Bacillus subtilis consists of two-component regulatory proteins, ComP (histidine kinase) and the response regulator, ComA, an extracellular pheromone (ComX), and a protein that is needed for the proteolytic cleavage and modification of pre-ComX (ComQ). ComQ and pre-ComX are both necessary and sufficient for the production of active pheromone, which is released as an isoprenylated peptide. Laboratory strain 168 and a number of natural isolates of bacilli differ in the primary sequences of their pheromones as well as in the masses of their isoprenyl adducts. We have shown that ComX, ComQ, and the membrane-localized sensor domain of ComP are highly polymorphic in natural isolates of bacilli all closely related to the laboratory strain of B. subtilis. In this study, we used two statistical tests (the ratio of synonymous and nonsynonymous substitution rates and the Tajima D test) to demonstrate that these polymorphic sequences evolved by diversifying selection rather than by neutral drift. We show that the choice of isoprenyl derivative is determined by the C-terminal (mature) sequence of pre-ComX rather than by the ComQ protein. The implications of these findings for the evolution of the quorum-sensing system and for the protein-protein interactions involved in determining specificity are discussed.
authors.affiliation: Public Health Research Institute and Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ansaldi
authors.forename: D
authors.initials: D
authors.lastname: Dubnau
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics / Q000254:growth & development*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational; D012641:Selection, Genetic; D016415:Sequence Alignment; D015398:Signal Transduction; D014166:Transferases / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial
chemical_list: D001426:Bacterial Proteins; C087040:ComX protein, Bacillus subtilis; D008565:Membrane Proteins; C070739:comQ protein, Bacillus subtilis; D014166:Transferases; C064995:comP protein, Bacillus subtilis