Optimised control of adaptive evolution with competing selective pressures

Abstract The development of methods to understand and control the population dynamics of microbial evolution remains an outstanding question in synthetic biology and biotechnology more broadly. Due to the stochastic nature of evolution, its limited observability, and complex intra-population dynamics, this presents a significant challenge. In this paper, we explore techniques to control the evolutionary dynamics of a population, based on manipulation of one or two orthogonal selective pressures, which may in turn be coupled to mutagenesis. Our approach builds on past research in evolutionary biology that developed frameworks to study intra-population variant competition during asexual adaptive processes (i.e. clonal interference). Extending this theory, we design optimal control strategies for one (or more) selective pressures that can be used to maximise the rate of adaptation across a population as a whole. We introduce a theoretical modelling framework for this process, which we support with both simulations and preliminary experimental data, providing a concrete basis for emerging control approaches to directed evolution and evolution-aware design.