Evolution Under Intrinsic Control is a blog entry at Mike Gene's The Design Matrix. Mike begins by noting that "antibiotic resistant bacteria has long been used as a classic example of Darwinian evolution in action." He then focuses on a study by Floyd Romesberg and colleagues which puts a new twist on the resistence theme. Quoting Mike:
The twist is this: in this case, mutations don’t “just happen” – bacteria make sure they happen. That is, the evolution of antibiotic resistance is not simply the passive process of selection screening through the available variability. On the contrary, bacteria respond to the insult by making sure there is a plentiful source of variability to screen.
In this study, it was determined that bacterial input was essential to the evolution of antibiotic resistance. In other words, the cellular process of “making sure there is a plentiful source of variability to screen” is exactly what is needed to evolve antibiotic resistance.
A key component to adaptation appears to be LexA; a DNA binding protein which performs a regulatory function affecting multiple genes. There is an ingenius structural strategy involving LexA and damaged DNA. The DNA damage detection process leads to a series of biochemical events, the end result of which, is to release the repression of genes whose expression then initiates repair of damaged DNA. Mike links to a paper titled Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance, published by PLOS Biology and authored by Ryan T. Cirz, Jodie K. Chin, David R. Andes, Valérie de Crécy-Lagard, William A. Craig, and Floyd E. Romesberg. Quoting from that paper:
The emergence of drug-resistant bacteria poses a serious threat to human health. In the case of several antibiotics, including those of the quinolone and rifamycin classes, bacteria rapidly acquire resistance through mutation of chromosomal genes during therapy. In this work, we show that preventing induction of the SOS response by interfering with the activity of the protease LexA renders pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results in the derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce resistance-conferring mutations.
Central to Darwinian views is the concept that mutations are random with respect to reproductive fitness. An efficient complex of genetic repair mechanisms ensures the integrity of cellular genomes. Mutations can be viewed as genetic changes which fall through existing DNA genomic integrity nets. Effective adaptation responses involve maintaining genomic integrity while allowing for some changes. That means maintaining stasis for functional and effective genes (most of them) while genetic tinkering occurs. Yet if genomic integrity is the consequence of a system, whose trigger mechanism ensures that only selective genes are expressed, then homeostatic capacity is intrinsically preprogrammed. When effective adaptive responses, resulting from genetic changes, act in concert with the types of mechanisms alluded to we have what Mike might describe as adjustments within homeostatic cellular environments. Quoting Mike:
While the teleological echo is faint, it is nevertheless there. We can begin to catch a glimpse of evolution as homeostasis. The integrity of the genome is threatened. Standard small scale feedback responses ensue as the cell attempts to reverse the change through repair and recombination mechanisms. But if the insult is too severe or too common, the next level of feedback response is…..evolution itself. The antibiotic is the stress that perturbs the homeostasis of the cells and evolution is the effector that reverses the effects of the change. Life fights back.
Mike concludes with the observation that DNA "may be plugged into an elaborate system that allows it act as sensor for its own continued perpetuation." Indeed. Or front loading DNA repair functions may be a sine qua non for cellular life forms.