Suppression by gene substitution for the leuD gene of Salmonella typhimurium.

recent review of suppression by GORINI and BECKWITH (1966) classifies A suppressors in terms df direct (intragenic or informational) and indirect suppression. In the former case the suppressor functions by causing an alteration in the mutated genes usually at the transcriptional or translational level. In the latter case the primary mutational lesion is circumvented without altering the mutated gene product. This report describes a case of indirect suppression in Salmonella typhimurium in which a suppressor mutation, at a locus (supQ) substantially distant from the leucine operon, results in the formation of a cytoplasmic product which can substitute for the product of a mutated leuD gene and thereby eliminate leucine auxotrophy. In the wild type, the leuD gene product normally forms a complex with the leuC gene product to form the isopropylmalate isomerase of the leucine biosynthetic pathway. The suppression of leuD mutations by supQ must therefore take place at the level of protein-protein interaction. The rather unusual pattern of suppressor specificity which results is also described and explained. Preliminary reports of this work were presented previously (KEMPER and MARGOLIN 1968a, 1968b). We will use bold face type to indicate the phenotype as illustrated in MATERIALS AND METHODS.