A genetic locus responsible for generalized high mutability in Escherichia coli.

Goldstein and Smoot' described a wild strain of Escherichia coli in which an abrupt change (spontaneous mutation?)leading to persistent genetic instability occurred during routine stock maintenance and transfer.The unstable strain ("Harvard" strain, ATCC #11887) did not differ obviously from its parent strain except in its very high frequency of "spontaneous" mutants (up to 15% of the total number of viable cells in a clonal population).Pathways for biosynthesis of purines, pyrimi- dines, amino acids, vitamins, and for fermentation of sugars were all affected.The nutritional requirements were in general single; however, the unusual genetic instability of the strain was seen to persist after a first mutation, so that double auxotrophs arose frequently.This high mutability was itself observed to be a stable hereditary property.Comparable instances of the actions of mutability factors or mutator genes have been reported in Drosophila,2 5 maize,6' I yeast,8 and Streptomyces.9In bacteria, Treffers and associates10-12 have described a similar case in Escherichia coli K-12.Elevated rates of mutation to resistance to antibiotics and bacteriophage and of reversion of auxotrophs were observed.Preliminary genetic studies by these authors and by Skaar'3 have indicated that this mutator gene lies in the vicinity of the leucine locus.Demerec et al.14 have reported a mutator gene in Salmonella typhimurium LT-7 that affects the stability of a variety of nutritional and resist- ance characters.Miyake"5 has mapped this determinant between the methionine and threonine loci.Elevated mutability in bacteria may also be caused by some form of interaction between the chromosome and an element of episomic or plastid nature.16, 17The present study concerns the demonstration in the Harvard strain of a discrete, chromosomal locus responsible for generalized high mutability, its transfer by sexual conjugation to E. coli K-12, its genetic mapping in this system, and its expression in K-12 strains.Materials and Methods.-Symbols:The fine structure and product of the determinant of high mutability in the Harvard strain being unknown, the term "gene" is avoided.To eliminate confusion with previously described mutability factors-i.e., M*,10 Mut,"3 mut,14 15 phage Mu1,16 transmissible element Mul7-the locus responsible for generalized genetic instability in the Har- vard strain will be designated ast, from the Greek ciaocaoa ("astasia" = instability, mutability).Strains carrying the locus will be termed ast+; those not so doing, ast-.