In this thread I would like to explore a specific paper written by Wright et al.
quote:Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5089-94. Hypermutation in derepressed operons of Escherichia coli K12. Wright BE, Longacre A, Reimers JM. Source
Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
This article presents evidence that starvation for leucine in an Escherichia coli auxotroph triggers metabolic activities that specifically target the leu operon for derepression, increased rates of transcription, and mutation. Derepression of the leu operon was a prerequisite for its activation by the signal nucleotide, guanosine tetraphosphate, which accumulates in response to nutritional stress (the stringent response). A quantitative correlation was established between leuB mRNA abundance and leuB- reversion rates. To further demonstrate that derepression increased mutation rates, the chromosomal leu operon was placed under the control of the inducible tac promoter. When the leu operon was induced by isopropyl-D-thiogalactoside, both leuB mRNA abundance and leuB- reversion rates increased. These investigations suggest that guanosine tetraphosphate may contribute as much as attenuation in regulating leu operon expression and that higher rates of mutation are specifically associated with the derepressed leu operon.
The full text (in .html format) can be found here.
Once the topic is promoted I will describe the methods used and the results in a way that a layperson can relate to. After this, we will determine if these findings demonstrate a process of random or guided mutation.
Just to get it out of the way, I define random mutations as changes in the DNA sequence that are blind to the needs of the organism. IOW, mutations are random with respect to fitness. I am not saying that mutation rates are constant through time, nor am I saying that each base has an equal chance of being substituted, inserted, or deleted. With respect to the paper, I will attempt to demonstrate that the same mechanisms that produce reversions in leuB- organisms will also cause deleterious mutations in very important and vital genes as well as mutations which do not change the fitness of offspring.