Rampant Reverse Evolution towards Specialization in Commensal Bacteria Colonizing the Gut

The maintenance of diversity in the gut microbiota is a signature of host health. Yet how strain variation emerges and changes over time in this ecosystem is poorly understood. Here we use a natural yet controlled system to track the effects of natural selection by the genetic signatures it leaves in evolving populations. By following the emergence of intra-species diversity in an Escherichia coli strain, we unravel a recurrent case of violation of Dollo’s law, which proposes that evolution is unidirectional and irreversible. We demonstrate de novo acquisition of a primordial lost phenotype via compensatory mutation and also genetic reversion, the latter leaving no trace of the past. We show that this reverse evolution generates two coexisting phenotypes, resource generalist and specialist, whose abundance can be controlled by diet supplementation. While specialists’ abundance is low, they avoid competition with the gut microbiota, whereas generalist abundance is dependent on microbiota composition. Our results highlight how a single genetic change can have large ecological consequences.