Predictability shifts from local to global rules during bacterial adaptation

The distribution of fitness effects of new mutations is central to predicting adaptive evolution, but observing how it changes as organisms adapt is challenging. Here we use saturated, genome-wide insertion libraries to quantify how the fitness effects of new mutations changed in two E. coli populations that adapted to a constant environment for 15,000 generations. The proportions of neutral and deleterious mutations remained constant, despite large fitness gains. In contrast, the beneficial fraction declined rapidly, approximating an exponential distribution, with strong epistasis profoundly changing the genetic identity of adaptive mutations. Despite this volatility, many important targets of selection were predictable from the ancestral distribution. This predictability occurs because genetic target size contributed to the fixation of beneficial mutations as much as or more than their effect sizes. Overall, our results demonstrate that short-term adaptation can be idiosyncratic but empirically predictable, and that long-term dynamics can be described by simple statistical principles. One-Sentence Summary Couce et al. demonstrate that short-term bacterial adaptation is predictable at the scale of individual genes, while long-term adaptation is predictable at a global scale. ### Competing Interest Statement The authors have declared no competing interest.