[This is just a teaser to get us started -- add to it, change it, throw it away, but please leave something worthwhile behind!]
John Cairn’s once observed that apparently non-growing populations of bacteria spontaneously acquire mutations which enable them to grow on a previously unutilizable carbon substrate.
An early explanation bordered on the metaphysical, invoking an awareness by the non-growing cell of the tantilizing substrate, lactose, and a consequent mutational targeting of a specific gene, lacZ, which, when appropriately modified, would allow growth on this compound.
Many requirements and predictions of this original model were quickly shown to be wrong. DNA replication occured in the “quiescent” cells, which were also growing, albeit at a slow rate. Mutations were not confined to the “targeted” gene alone. Adaptation to growth on lactose would not occur if the gene were on the chromosome; the observed reversion to lactose utilization was only seen when lacZ was on a specialized F plasmid. Additionally, the effect was found only if this plasmid expressed a suite of functions which enabled plasmid replication by rolling-circle synthesis of single-stranded DNA and resulting transfer of this DNA to recipient cells.
Cairn’s descendents have bifurcated two basic models from the original, although a number of others have been left lying in the dust over the years. Both assume that an evolved mechanism senses stress (i.e.,starvation) and directs an increase in mutagenesis. Pat Foster’s model asserts that stress induces rpoS, which in turn makes recombination mutagenic. Susan Rosenberg’s model maintains that a general hyper-mutagenic state is evoked which is independent of rec functions.
We point out that a third model exists which makes no assumption of any evolved stress-sensitive mutagenic mechanism, but instead relies on the bag of genetic tricks described and well verified over the last century. We note that Cairn’s cells are growing slowly, and are replicating their DNA. Duplications in DNA are relatively common and can be amplified during replication. A defective gene which nevertheless sustains slow growth allows an increase in the basal growth rate when duplicated. Selection for faster growth will favor cells containing higher order amplifications of the defective gene. Such cells will sweep the population. The opportunity for true reversion will be roughly the number of such cells times the average amplification factor times the rate of reverting a single gene per generation. Because the amplification factor is under selection and expected to grow with the number of generations, the probability of true reversion to lac+ will increase substantially over the course of the experiment, accounting for all colonies observed.
We like this hypothesis because it involves no new technology, no magic, and no religion. We have a substantial amount of data supporting it. The requirement that the defective locus be on an F derivative is easily understood by two facts: One, the relatively small region of interest is flanked by exact copies of the insertion element, IS3, which allows easy initial duplication of the region. Two, F is constantly replicating itself by a rolling-circle mechanism generating long single strands. These can induce rearrangements by recombination or annealing. Under selection, this can lead to rapid increase in the degree of amplification, and promote remodeling leading to diminished size of the amplified element, thus minimizing the cost of ancillary gene dosage effects.-- Eric Kofoid