The adaptive acquisition of single DNA segments drives metabolic evolution across E. coli lineages

Even closely related prokaryotes show an astounding diversity in their ability to grow in different nutritional environments1,2. Mechanistically, this diversity arises predominantly through horizontal gene transfer, the exchange of DNA between individuals from different strains3. It has been hypothesized that complex metabolic adaptations - those requiring the acquisition of multiple distinct DNA segments - can evolve via selectively neutral intermediate steps4,5; an alternative explanation rests on the existence of intermediate environments that make each individual DNA acquisition adaptive6 However, it is unclear how important changing environments6 are compared to neutral explorations of phenotype space5; more fundamentally, it is unknown what fraction of metabolic adaptations are indeed complex. Here, we use metabolic network simulations to show that all 3,363 phenotypic innovations observed in the evolutionary history of 53 E. coli strains arose through the acquisition of a single DNA segment; while we found no evidence for the contribution of selectively neutral processes, 10.6% of adaptations to previously unviable environments relied on the support of DNA acquisitions on earlier phylogenetic branches. 97.0% of all metabolic phenotypes accessible for the E. coli pan-genome could be bestowed on any ancestral strain by transferring a single DNA segment from one of the extant strains. These results demonstrate an amazing ability of the E. coli lineage to quickly adapt to previously inaccessible environments through a single DNA acquisition, an ability likely to be mirrored in other clades of generalist bacteria.