Origin of Mutations During Growth Under Selection

John Paul J. Aboubechara


Natural selection requires heritable variation in populations to select individuals of increased fitness.  While natural selection is well understood, the development of variation remains controversial.  Classical experiments in Escherichia coli demonstrated that variation arises from mutations that occur spontaneously and without the influence of selective stresses.  However, those experiments made use of lethal antibiotics-resistance assays that cannot detect growth and the presumably small effects of selection.  Current research systems study the role of selection using non-lethal nutrient starvation.  Starvation on lactose yields a 100-fold higher mutation rate than expected. Thus, under starvation conditions, selection seems to be mutagenic and allows for sudden adaptation. In contrast, we consider that the appearance of Lac+ colonies on selective media depends on common variants with high copy numbers of the leaky lac gene to slowly initiate growth under selection. This work investigates the role of growth temperature and nucleases on adaptive mutation by assaying the frequency of Lac+ revertants at various temperatures and in nuclease mutants, respectively. We conclude that the temperature dependence of Lac+ reversion may be due to the temperature sensitivity of plasmid transfer functions. Further, nucleases appear to inhibit Lac+ reversion and adaptive mutation in general.   

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