The effect of population structure and the mode of selection on multi-locus adaptation Restricted; Files & ToC

Abstract

Evolution is influenced by many factors, for example, epistasis, sex, and mutation. This thesis investigates key factors influencing evolution, including effect of population structure and mode of selection with multiple loci. 

The first part explores adaptation in structured populations with clonal interference by introducing drastic population dynamics and synchronized sexual reproduction.  This approach effectively utilizes genetic diversity preserved by population structure, leading to enhanced adaptation. Surprisingly, the rate of adaptation in structured populations is comparable to that in well-mixed populations, even in a consistent environment.

The second part focuses on the impact of modifying the fitness function to simulate effective population structure. By imposing limits on the fittest individuals using a logistic fitness function, moderately fit individuals are promoted, resulting in increased genetic diversity and accelerated adaptation in sexual populations.  This finding highlights the importance of considering the fitness distribution in shaping the adaptive process. 

In the third part, a simulation analysis is applied to investigate the emergence of variants of concern (VOCs) in SARS-CoV-2. A quantitative framework captures evolutionary pathways, considering both between-host transmission and within-host chronic infections. Results suggest that VOCs are primarily driven by multiple mutations from individuals with acute or chronic infections. Addressing chronic infections becomes vital in reducing future VOC emergence. Our findings have implications for optimal evolution strategies with clonal interference, evolutionary experiments, epidemic disease analysis, and future pathogen prediction. 

Table of Contents

This table of contents is under embargo until 16 August 2025

About this Dissertation

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School	Laney Graduate School
Department	Physics
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Evolution and Development
Keyword	fitness landscape SARS–CoV–2 evolution population structure clonal interference
Committee Chair / Thesis Advisor	Daniel B. Weissman, Emory University
Committee Members	Katia Koelle, Emory University Stefan Boettcher, Emory University Minsu Kim, Emory University Ilya Nemenman, Emory University

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