Abstract:

Comparative genomics reveals an unexpected diversity in the molecular mechanisms underlying conserved cellular functions, such as DNA replication and cytokinesis. However, the genetic bases and evolutionary processes underlying this “molecular diversity” remain to be explained. Here, we review a tool to generate alternative mechanisms for conserved cellular functions and test hypotheses concerning the generation of molecular diversity: evolutionary repair experiments, in which laboratory microbial populations adapt in response to a genetic perturbation. We summarize the insights gained from evolutionary repair experiments, the spectrum and dynamics of compensatory mutations, and the alternative molecular mechanisms used to repair perturbed cellular functions. We relate these experiments to the modifications of conserved functions that have occurred outside the laboratory. We propose experimental strategies, especially those that establish a quantitative understanding of compensatory mutations and alternative molecular mechanisms, to improve evolutionary repair as a tool to explore the molecular diversity of life.