The Emergence, Maintenance, and Diversity of Strains in Microbial Pathogen Populations

Author

• Brandon P. Ely, The Graduate Center, City University of New YorkFollow

Date of Degree

6-2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Biology

Advisor

Weigang Qiu

Committee Members

Sebastian Alvarado

John Dennehy

Dustin Brisson

Chunhao Li

Subject Categories

Biodiversity | Bioinformatics | Biotechnology | Computational Biology | Evolution | Genomics | Immunology of Infectious Disease | Molecular Genetics | Population Biology

Keywords

Borrelia, Lyme, bioinformatics, epigenetics, evolution

Abstract

Microbial pathogens often exist as structured populations of genetically and ecologically distinct lineages, commonly referred to as strains. These strains persist despite frequent recombination and genetic exchanges, raising an important question in evolutionary epidemiology: how do pathogen strains emerge, persist, and maintain distinct identities? Using a combination of theoretical modeling, simulation, and comparative genomics, I investigate how immune selection, ecological interactions, and epigenetic variation contribute to the emergence and maintenance of diversity in microbial pathogen populations, with a particular focus on the Lyme disease pathogen Borrelia burgdorferi.

Using both mathematical and agent-based modeling, I developed frameworks for simulating evolution with genetic algorithms to explore how natural selection facilitates strain emergence. First, I demonstrate how selection for sequence novelty, necessary for immune escape, relaxes mutational constraints and facilitates the emergence of high fitness variants by simulating evolution across empirically generated fitness landscapes. I then model a vector-host-pathogen transmission cycle to test the two main hypotheses for Borrelia population structuring: negative frequency dependence driven by host immunity and multiple niche polymorphism via host adaptation. The outcomes of these simulations unify the two hypotheses, suggesting that both immune selection and multiple niche polymorphism act jointly as forces shaping natural Borrelia populations. Finally, I look at how strains can maintain their identity despite opportunities for genetic exchange. Through phylogenetic analyses and nanopore sequencing, I reveal the restriction-modification system repertoires across the Borrelia genus, their evolutionary history, and their DNA target specificities. Diversification within the target specificity domains of restriction-modification enzymes, supported both by signals of positive selection and variation in identified 6mA DNA target motifs, is a likely consequence of selective pressure for anti-phage defense and results in distinct strain-level epigenetic profiles with potential for restricting gene flow within populations.

Together, these results demonstrate that strain structure emerges from an interaction of immune-mediated diversification, ecological specialization, and genomic mechanisms that shape routes of gene flow within populations.

Recommended Citation

Ely, Brandon P., "The Emergence, Maintenance, and Diversity of Strains in Microbial Pathogen Populations" (2026). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/6758