title: Evolution of a new gene substituting for the leuD gene of Salmonella typhimurium: origin and nature of supQ and newD mutations.
abstract: The second specific enzyme in the biosynthesis of leucine, alpha-isopropylmalate isomerase, is coded for by two genes, leuC and leuD. Leucine auxotrophs carrying mutations in the leuD gene (including deletions of the entire leuD gene) revert to leucine prototrophy by secondary mutations at the locus supQ, which is located in the proline region of the chromosome. The mechanism of the supQ function is explained by the following model. The supQ gene and an additional gene, newD, code for two different subunits of a multimeric enzyme, whose normal function is yet to be determined. The newD gene protein is able, without genetic alterations, to form an active complex with the leuC protein, thus replacing the nonfunctional or missing leuD protein and restoring leucine prototrophy. The newD protein has, however, a higher affinity for the supQ protein than for the leuC protein; therefore, mutations in the supQ gene are needed to make sufficient amounts of the newD protein available. The following gene order has been established: gpt-proB-proA-ataA-supQ-newD. Different supQ mutations have been identified, i.e., insertion in the supQ gene, point mutations, and deletions of various extent. Some deletions remove the P22 phage attachment site ataA. Other supQ deletions are simultaneously Pro(-), because they extend into the proA or proA and proB genes; some extend even further, i.e., into the gpt gene (guanine phosphoribosyl transferase). Mutations in the newD gene caused renewed leucine auxotrophy in leuD supQ mutant strains. One newD mutation causes a temperature-sensitive Leu(+) phenotype. Alternate models for the supQ-newD interactions are discussed.
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005796:Genes; D008040:Genetic Linkage; D007930:Leucine / Q000378:metabolism*; D008242:Lysogeny; D008954:Models, Biological; D009153:Mutagens; D009154:Mutation; D009604:Nitrosoguanidines; D011392:Proline / Q000378:metabolism; D012483:Salmonella Phages; D012486:Salmonella typhimurium / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D009153:Mutagens; D009604:Nitrosoguanidines; D011392:Proline; D007930:Leucine; D000225:Adenine