Some puzzling observations on heat-induced transversion mutagenesis in bacteriophage T4


A question of some interest in the early decades of genetics was whether the nondividing gene could mutate spontaneously. This question was sidelined when attention switched to the induction of mutations, first by ionizing irradiation, then by ultraviolet irradiation, and finally by chemical agents. The matter was revived by Schr6dinger's (1944) unfortunate attribution of an almost mystical stability to the gene. The first convincing experimental attack on the question was mounted by Lotte Auerbach (1959), who demonstrated that dry Neurospora crassa spores accumulate mutations during storage. The issue then fell silent again for several years until a moment in the middle 1960s when one of us (J. W. D.) decided to take a shortcut and perform some reversion experiments using stocks of bacteriophage T4 rll mutants that had been stored for a few years in the refrigerator. T4 stocks can be very stable, and quick-and-dirty experiments are quite feasible using stocks several years old. In this instance, however, J. W. D. noticed that revertant frequencies in some of the stocks had risen substantially. Subsequent work established several genetic and kinetic parameters of this mutation process. First, only G:C base pairs mutate spontaneously in extracellular T4 particles (Drake 1966). Second, both transitions and transversions occur (Drake and McGuire 1967). The transitions are produced by the deamination of the 5-hydroxymethylcytosine residues that comprise 'C' in T4 DNA (Baltz et al. 1976). The transversions arise by a spontaneous chemical event targeting G residues (Bingham et al. 1976) and seem to consist exclusively of G:C---* T:A (Kricker and Drake 1990). The premutagenic lesion generating transversions seems to mispair only infrequently (less than 10% per replication) (Ripley 1988, describing heat-mutagenesis experiments performed some years earlier at the University of Illinois, Urbana-Champaign). Oxygen-mediated mutagenesis can occur via the production of 8-oxoguanine, which can pair correctly with C or incorrectly with A to produce the transversion G:C--* T:A and which is subject to diverse repair processes and frequent

DOI: 10.1007/BF02994696

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@article{Drake2008SomePO, title={Some puzzling observations on heat-induced transversion mutagenesis in bacteriophage T4}, author={John W. Drake and Leslie A. Smith}, journal={Journal of Genetics}, year={2008}, volume={78}, pages={3-5} }