Modeling adaptive dynamics in microbial populations with applications to the evolution of cellular resource allocation trade-offs

Adaptive evolution is the process by which natural selection, acting on variation within a population, promotes the survival of individuals that are more successful at reproducing and contributing to future generations. Evolutionary processes in microbes occur at the intersection of population genetics, natural selection, and underlying mechanistic constraints, to give rise to the repertoire of adaptation observed in nature. Understanding microbial adaptive evolution is of critical importance for human health for example, through the emergence of pathogenicity and antibiotic resistance. Moreover, the stability and function of natural and artificial ecosystems is contingent on the evolving interactions between microbes, and between microbes and the environment. We present a modelling framework, based on the theory of adaptive dynamics, to investigate how cellular resource allocation trade-offs affect the adaptation process. We used resource-consumer theory, which explicitly models the interactions between cells and their environment, together with matrix models of structured populations, to implement phenotype-determined cellular strategies of resource allocation between mutually exclusive processes. We then analyse the outcome of competitions between different phenotypes across environmental and competitive conditions. We applied our methods to the evolution of strategies (phenotypes) for resource allocation between two competing cellular process in microbial populations growing in chemostat-like environments. We calculated the adaptively stable strategies for several models and showed how state-structured population models can be mapped to simpler chemostat models on invariant manifolds. We then extended our analysis to the case where a limiting nutrient may be utilized using two alternative metabolic pathways. We described how the total population fitness of a metabolic strategy can be constructed from the individual decisions of its constituent members. We developed numerical methods to simulate and analyse general models of adaptive dynamics using principles from graph theory and discrete Markov processes. The methods were used to explore the evolution of nutrient use strategies for microbial populations growing on two and three substitutable nutrients. We highlight the importance of the ancestral phenotype in channelling the adaptation process, which, together with the choice of the mutational kernel, influences the adaptively stable strategies and modes of co-existence. In a related finding, we show how some phenotypes are adaptively stable only in the presence of a competitor lineage that modifies the environment in a manner that permits another phenotype to invade. Our methods also reveal instances where historical contingency and chance have an important effect on determining the stable nutrient use strategies. Finally, we demonstrate the existence of adaptively stable periodic solutions whereby, under some conditions, phenotype successions are cyclical. Our work builds on the foundation of adaptive dynamics theory to provide a general framework for analysing models of microbial adaptation. We focused on understanding the implications of underlying constraints and cellular resource allocation trade-offs in the context of adaptive evolution

Predicting metabolic adaptation from networks of mutational paths

The structure and dynamics of microbial communities reflect trade-offs in the ability to use different resources. Here, Josephides and Swain incorporate metabolic trade-offs into an eco-evolutionary model to predict networks of mutational paths and the evolutionary outcomes for microbial communities

Modeling the evolution of a classic genetic switch

Abstract Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution