INSTABILITY OF A MISSENSE SUPPRESSOR RESULTING FROM A DUPLICATION OF GENETIC MATERIAL

A number of spontaneously arising suppressor mutations of the trpA36§ mutation (an arginine for glycine replacement in the tryptophan synthetase A protein of Escherichia coli) have been isolated. All map at or near the same genetic locus (linked to argH) as the trpA36 suppressors described by Brody & Yanofsky (1965); they differ from the Brody-Yanofsky suppressor isolates by their slower growth rates in minimal medium, their death following a shift-up from minimal medium to Tryptone, and their failure to segregate Trp- cells. Our experiments suggest that these new suppressed isolates are haploid for the suppressor gene and that the Brody-Yanofsky suppressed strains are partially heterozygous for at least the suppressor locus i.e. (su+/ su-). Transduction of the new suppressors, by phage P1, occasionally yield fast-growing, Tryptoneinsensitive and genetically unstable suppressed clones. This is due to formation of a partial heterozygote analogous to the Brody-Yanofsky suppressors. In one strain the partial heterozygosity included the linked metB, argH and thi loci. Interrupted mating experiments established that both copies of the duplication are integrated within the bacterial chromosome: the segregation patterns of the duplicated markers suggest that the duplications are in tandem and that segregation usually occurs by a single crossover between copies of the duplication, thereby causing elimination of one set of the duplicated genes. The slow growth and sensitivity to enriched media of the haploid suppressor strains may be due to the loss of the wild-type suppressor gene function. © 1969.