Parallel evolution of mutational fitness effects over 50,000 generations

Abstract

Over evolutionary time, bacteria face changing environments, which may require different sets of genes for survival. As they adapt to a specific constant environment, some genes are modified and lost, which can increase fitness while also modulating the effects of further gene losses. However, whether evolutionary specialization leads to systematic changes in robustness to gene loss is largely unexplored. Here, we compare the effects of insertion mutations in Escherichia coli between ancestral and 12 independently derived strains after 50,000 generations of growth in a simple, uniform environment. We find that epistasis between insertion mutations and genetic background is common, but the overall distribution of fitness effects is largely unchanged. In particular, we see systematic changes in gene essentiality, with more genes becoming essential over evolution than vice versa. The resulting changes often occurred in parallel across the independently evolving populations. A few of the changes in gene essentiality are associated with large structural variations, but most are not. Taken together, our results demonstrate that gene essentiality is a dynamic, evolvable property, and they suggest that changes in gene essentiality are a result of natural selection in this long-term evolution experiment, rather than a mere byproduct of structural changes.

Predictability shifts from local to global rules during bacterial adaptation

“…A potentially important difference is that the fitness variation among the yeast backgrounds was generated by crossing two distantly related strains, whereas we use a series of backgrounds from lineages undergoing adaptation to the same environment in which we assess the fitness effects of the new mutations. As further support for our findings, a companion study focused on the evolution of gene essentiality in the LTEE found no systematic changes in deleterious effects across all of the lineages at 50,000 generations ( 29 ). In any case, theoretical predictions about the tail of deleterious mutations differ substantially and have been guided mostly by plausibility arguments ( 14, 15 ), and so all of these studies should help refine current models by clarifying the assumptions and narrowing the range of parameters.…”

Resolving deleterious and near-neutral effects requires different pooled fitness assay designs

“…Like the error bounds estimated before, we observe that errors are consistently larger for more deleterious mutations (Fig 1B). We turned to a deeply sequenced transposon sequencing dataset of E. coli B REL606 from our previous work (Limdi et al, 2022). We found a statistically significant negative correlation between the estimated fitness of disrupting a gene and the error in the estimate ( p -value < 0.001, Fig 1C); this pattern was more evident when we binned by mutant effect sizes (Fig 1D).…”

High-throughput transposon mutagenesis in the family Enterobacteriaceae reveals core essential genes and rapid turnover of essentiality

“…CRISPRi screens in diverse E. coli strains have shown that gene essentiality varies widely between strains, and that phylogenetic distance is a poor predictor of the fitness effect of any particular gene (20); similar observation have been made using transposon mutagenesis in a collection of Pseudomonas aeruginosa strains (18). Even during a relatively short period of adaptation to a static environment, recent work investigating gene essentiality in the Long-Term Evolution Experiment (LTEE) found nearly two hundred genes that change in essentiality status (81). Here, we had initially expected to identify genus-specific essential genes but were unable to support this with our TraDIS dataset.…”