Changing fitness effects of mutations through long-term bacterial evolution

The distribution of fitness effects of new mutations shapes evolution, but it is challenging to observe how it changes as organisms adapt. Using Escherichia coli lineages spanning 50,000 generations of evolution, we quantify the fitness effects of insertion mutations in every gene. Macroscopically, the fraction of deleterious mutations changed little over time whereas the beneficial tail declined sharply, approaching an exponential distribution. Microscopically, changes in individual gene essentiality and deleterious effects often occurred in parallel; altered essentiality is only partly explained by structural variation. The identity and effect sizes of beneficial mutations changed rapidly over time, but many targets of selection remained predictable because of the importance of loss-of-function mutations. Taken together, these results reveal the dynamic—but statistically predictable—nature of mutational fitness effects. The benefits and costs of mutations that undergo natural selection can change depending on genetic interactions with subsequent mutations. In an enduring experiment, 12 lineages of Escherichia coli have been maintained for more than 75,000 generations, with each generation sampled and preserved. Couce et al. made transposon insertion libraries in ancestral and evolved strains taken at the 50,000 generation point and measured fitness in competition experiments using these samples. The numbers of beneficial mutations rapidly tailed off during long-term passage, with parallel changes in fitness cost and gene essentiality occurring across the lineages. The authors found nonessential genes that became essential and essential genes that became nonessential in all lineages. Predictability stemmed from the importance of loss-of-function mutations that scale with the length of the target genes. —Caroline Ash Predictable and parallel changes occur in the fitness effects of mutations in Escherichia coli over 50,000 generations.