Adaptive evolution of complex metabolic innovations

A central challenge in evolutionary biology concerns the mechanisms by which complex metabolic innovations arise. In many cases, metabolic innovations depend on the simultaneous acquisition of multiple reactions that individually provide little or no benefit in the given environment. It has been argued that complex adaptations may arise through the non-adaptive exploration of phenotype space, but such processes lack empirical evidence and are expected to be too slow to explain the metabolic diversity observed even among closely related bacterial species. We propose the dynamic environment model, where adaptive innovations accessible through the addition of a single reaction serve as stepping stones towards the later establishment of complex metabolic features in another environment. Thus, temporally varying nutrient conditions accelerate the adaptive expansion of metabolic networks. We demonstrate the feasibility of this model through three complementary analyses. First, we show in silico that E. coli can adapt to novel metabolic environments by using “intermediate” environments as adaptive stepping stones. Second, by reconstructing the evolutionary history of horizontal gene gains in bacterial species, we demonstrate that complex metabolic pathways are indeed established in a defined order as predicted by the dynamic environment model. Third, we show experimentally how the adaptation of laboratory populations of E. coli to one carbon source facilitates the later adaptation to another carbon source. Our work thus demonstrates how complex innovations can evolve through series of adaptive steps without the need to invoke non-adaptive processes.