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Title: Modeling adaptive dynamics in microbial populations with applications to the evolution of cellular resource allocation trade-offs
Author: Josephides, Christos
ISNI:       0000 0004 6059 3506
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2016
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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.
Supervisor: Swain, Peter ; Brown, Sam Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: evolution ; mathematical modeling