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Author ORCID Identifier

https://orcid.org/0000-0002-5501-2573

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2020

Month Degree Awarded

May

First Advisor

Li-Jun Ma

Second Advisor

John Gibbons

Third Advisor

Lillian Fritz-Laylin

Fourth Advisor

Peter Chien

Subject Categories

Bioinformatics | Genomics

Abstract

The presence of accessory chromosomes is one of the most fascinating features in the genomes of Fusarium oxysporum (Fo) species complex that includes both plant and animal pathogens. In plant-pathogenic Fo strains, these accessory chromosomes govern host-specific pathogenicity through unique sets of virulence factors, including secreted effectors and plant cell wall degrading enzymes, while the identity of such factors are largely unknown in human infecting strains. This dissertation is composed of three projects that focused on studying the gene composition and transcriptional regulation of human-pathogenic Fo strains. The first project deciphered the genome of the clinical Fo strain, NRRL 32931, compared its genetic composition and transcriptional profiles with the tomato-infecting strain, Fol4287. At the genomic level, we identified unique accessory chromosomes that were enriched in genes associated with ion transport and homeostasis. Genotype, but not phenotype results, indicated strains respond and adapt to pH differently.


Transcriptomic analysis found distinct gene regulations under acidic and alkaline conditions which matched their unique gene content. The second project focused on the PacC/Rim101 gene family expansion in NRRL 32931. PacC encodes a pH responsive transcription factor implicated in alkaline pH response in higher fungi. Phenotypic characteristics under stress conditions and transcriptome profiles at alkaline pH were compared between core and accessory PacC gene knockouts. The core PacC_o had a broader impact on biological processes, while the accessory PacC_b was limited to lipid metabolism and ion transport. Phenotypes and differentially expressed genes from the two mutants shared similarities but large differences, indicating independent roles of accessory PacC. For the last project, we sequenced the genomes of two other clinical isolates, which displayed a certain degree of conservation in the accessory chromosomes and found one isolate having further PacC gene expansion. Accessory PacC genes were also detected in over 10 clinical Fo isolates that belonged to different lineages, indicating the importance and prevalence of PacC genes. In summary, my research not only confirmed the presence of accessory chromosomes among the genomes of human infecting Fo strains, but also demonstrated the functional importance of genes encoded in these accessory chromosomes in adapting to human hosts.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Saturday, May 08, 2021

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