Tandem genetic duplications in Salmonella typhimurium: Amplification of the histidine operon

R. Philip Anderson, John R. Roth

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28 Scopus citations


Salmonella strains harboring tandem duplications of chromosomal segments including the histidine operon may be selected from populations of hisO promoter-like mutants. The twofold increase in gene dosage of the histidine operon caused by tandem duplication provides resistance to concentrations of the histidine analogue 3-amino-1,2,4-triazole that inhibit the growth of haploid hisO mutants. Several properties of AT-resistant mutants indicate that they harbor tandem chromosomal duplications: (i) the AT-resistant phenotype of these strains is genetically unstable. Such instability is dependent upon a functional recombination system, (ii) AT-resistant mutants express approximately twice the levels of his enzymes as parental strains. (iii) Genetic tests indicate that AT-resistant mutants are merodiploid for large segments (up to 26%) of their genome. (iv) For certain isolates, the merodiploid and AT-resistant nature of these strains are properties cotransducible with a distant chromosomal marker unrelated to the his operon. We interpret these results as indicating cotransduction of the join-point of a tandem duplication with this distant marker. The spontaneous frequency of tandem his duplications is remarkably high (6·2 × 10-5 per cell). This frequency is more than 6000-fold reduced in recA- genetic backgrounds. Two major types of tandem his duplications are repeatedly isolated, having an identical ~13% or ~22% of their genome duplicated, respectively. When duplication-containing strains are grown under conditions that select for resistance to increased AT concentrations, clones harboring additional tandem copies (amplification) of the his operon are obtained. The role which such gene amplification may play in bacterial adaptation is discussed.

Original languageEnglish (US)
Pages (from-to)53-71
Number of pages19
JournalJournal of Molecular Biology
Issue number1
StatePublished - Nov 25 1978
Externally publishedYes

ASJC Scopus subject areas

  • Virology


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