The origin of the logic of adaptive mutations: standing by to grow again.

For decades, discussions about the evolution of species overlooked microorganisms. Over a century ago, Neisser and Massini isolated a coliform bacterium that appeared to acquire mutations adapting it to its environment, naming it Bacterium coli mutabile to reflect this feature. With the advent of molecular biology, these widely debated experiments were subsequently forgotten. Here, we present the history of an experiment that reproduces their observations in a modern context where it has become possible to identify the nature of these mutations down to the nucleotide level. Its findings demonstrate that the transcription of gene families that ensure the long-term maintenance of the metabolism of ageing cells is a direct source of adaptive mutations: this process enables bacteria to identify previously unexploited environmental factors that can now support growth. We propose that the driving force behind this adaptation is the spontaneous dehydration/deamidation of polypeptide chains, which dictates an intrinsic lifespan for every protein. This universal mechanism of inevitable protein ageing necessitates their re-synthesis to maintain their function; however the transcription process, which involves opening the DNA double helix, is locally mutagenic. Thus, as bacteria age, the continuous re-synthesis of some of the proteins that perform the functions enabling survival triggers a local mutagenic process. This yields genetic variants, some of which may be beneficial and are therefore retained.