Date of Award

Winter 2020

Project Type

Dissertation

Program or Major

Molecular and Evolutionary Systems Biology

Degree Name

Doctor of Philosophy

First Advisor

Cheryl P Andam

Second Advisor

W. Kelley Thomas

Third Advisor

Matthew MacManes

Abstract

Bacterial populations are extraordinarily heterogeneous. Despite growing clonally, these populations are often composed of multiple lineages distinguished by both phenotypic and genetic differences that are caused by both allelic and whole gene variation. Such genomic mosaicism and within-species variation can significantly impact a species’ response to selective pressures from antibiotic use, vaccination, immune responses and host environment. One important process that contributes to this phenomenon is recombination, the exchange of very similar DNA sequences between strains which can result to either the addition or replacement of homologous genes. Current models of microbial recombination incorporate the null expectation that recombination is a homogeneous process across a species, whereby different lineages of the same species and different genes within a genome exhibit the same rates of DNA donation and receipt. However, recent work has demonstrated that intra-species recombination rates can differ even between strains. This dissertation attempts to elucidate the extent of, and the processes underlying, heterogeneity in genomic content in microbial species and populations relevant to human health. The first chapter addresses the best-known producer of the tetracycline class of antibiotics, Streptomyces rimosus. Results suggest that even strains appearing nearly identical in a core-genome phylogeny have divergent biosynthetic gene cluster content, emphasizing the importance of analyzing entire populations in drug discovery protocols. The second chapter explores the population dynamics of one of the most common causes of foodborne illness in the world, Salmonella enterica with results that indicate the evolution of ecologically unique subspecies of S. enterica are intricately linked by heterogeneous recombination. The third and fourth chapters demonstrate similar patterns of genomic diversity and recombination of clinically relevant genes in populations of Campylobacter jejuni and S. enterica collected from hospitals in New Hampshire in 2017. Finally, the fifth chapter describes a novel bioinformatic program called HERO which rapidly identifies and visualizes donor-recipient recombination pairs from a bacterial population. It also reports measures of heterogeneity in the population’s total recombination including events per donor-recipient pair, recombined DNA fragment length and the number of events per gene. Collectively, these results contribute to the growing evidence that intra-species heterogeneity plays a role in the evolution and management of bacterial species associated with public health.

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