Second-order selection for evolvability predicts winners in a large E. coli population

In theory, competition between asexual lineages can lead to second-order selection for greater evolvability. To test this hypothesis, we revived a frozen population of Escherichia coli from a long-term evolution experiment and compared the fitness and ultimate fates of four genetically distinct clones. Surprisingly, we found that two clones with beneficial mutations that would eventually take over the population had significantly lower competitive fitness than two clones with mutations that later went extinct. By replaying evolution many times from these clones, we show that the eventual winners prevailed because they had greater potential for further adaptation. Antagonistic epistatic interactions that reduce the benefit of certain regulatory mutations in the eventual losers explain, at least in part, why they were ultimately outcompeted.