The topic today is directly central to “gene-environment interactions.” Three decades ago, experiments in the lab of John Cairns showed that the effect of “environmental stress” on the mutation rate in bacteria can be remarkably strong (the “stress” they used was “to withhold an important nutrient). Those findings are relevant to evolution: as a species evolves in any niche on the planet, it will “sense” environmental signals (both beneficial and adverse conditions), and a mechanism must be in place to alter the DNA sequence (i.e. mutations) in relevant genes –– in order for that species to survive (i.e. find food, avoid predators, and reproduce). These gene-environment interactions can be studied in malignant tumors, as well as in bacteria, and the basic mechanisms are more or less the same similar.
More recent bacterial experiments are consistent the older findings. For example, there is plenty of evidence that various antibiotics increase mutation rates –– when the antibiotic is used at sub-inhibitory concentrations. It is therefore suggested that such treatments promote “resistance evolution,” because they enhance the process of genetic variation on which natural selection can act. However, existing methods to calculate the mutation rate fail to consider the effect of these environmental stress signals on “rate of death” or on population dynamics.
Developing new experimental and computational tools, authors [see attached publication] find that taking death into account significantly lowers the signal for stress-induced mutagenesis. Furthermore, authors show treatments that increase mutation rate do not always lead to increased genetic diversity –– which questions the standard paradigm of increased evolvability under stress. Most of the controversy surrounding Cairns’ original experiments initially came from the question of whether these mutations were Lamarckian [Lamarck (1744-1829) proposed that an organism can pass on, to its offspring, characteristics –– that it has acquired through use or disuse during its lifetime. The oft-used example is “the neck of giraffes became longer because they needed to eat leaves higher in trees during times of drought), i.e. do these mutations arise at higher rate when cells “sense” that such mutations would be beneficial? However, many additional experiments quickly suggested that this phenomenon can be explained by more standard Darwinian mechanisms (i.e. genetic changes are not targeted, but rather occur randomly, and then are either selected for, or rejected).
Authors state convincingly that “measuring mutation rates under stress is problematic, because existing methods do not take into account death.” Authors (correctly) insist that sub-inhibitory stress levels can induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size –– thus providing more opportunities to acquire further mutations. They show that ignoring death leads to a systematic over-estimation of mutation rates under stress. Using a system based on plasmid segregation that allows one to measure death and division rates simultaneously in bacterial populations, authors showed that a substantial death rate occurs at the tested sub-inhibitory concentrations previously reported to increase mutation rate. Taking this death rate into account –– lowers (in fact, sometimes removes) the signal for stress-induced mutagenesis. In summary: [a] population dynamics and, in particular, the numbers of cell divisions, are crucial but neglected parameters in the evolvability of a population; [b] providing experimental and computational tools and methods to study evolvability under stress, authors propose that the magnitude and significance of the stress-induced mutagenesis paradigm needs to be reassessed.
PLoS Biol May 2o18; 16: e2005056