Seeking Goldilocks During Evolution of Drug Resistance

Speciation can occur when a population is split and the resulting subpopulations evolve independently, accumulating mutations over time that make them incompatible with one another. It is thought that such incompatible mutations, known as Bateson-Dobzhansky-Muller (BDM) incompatibilities, may arise when the two populations face different environments, which impose different selective pressures. However, a new study in PLOS Biology by Ono et al. finds that the first-step mutations selected in yeast populations evolving in parallel in the presence of the antifungal drug nystatin are frequently incompatible with one another. This incompatibility is environment dependent, such that the combination of two incompatible alleles can become advantageous under increasing drug concentrations. This suggests that the activity for the affected pathway must have an optimum level, the value of which varies according to the drug concentration. It is likely that many biological processes similarly have an optimum under a given environment and many single-step adaptive ways to reach it; thus, not only should BDM incompatibilities commonly arise during parallel evolution, they might be virtually inevitable, as the combination of two such steps is likely to overshoot the optimum.