Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item THE EVOLUTIONARY TRAJECTORY OF METARHIZIUM ROBERTSII ENDOPHYTIC CAPABILITY AND ENTOMOPATHOGENICITY(2024) Sheng, Huiyu; St. Leger, Raymond; Entomology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Metarhizium fungi are a keystone genus of soil-inhabiting ascomycetes providing essential ecosystem services as saprotrophs, plant symbionts and insect pathogens, among other roles. Recent studies have looked at how Metarhizium niches have evolved and shaped genome evolution over large time scales within the Metarhizium genus. This dissertation uses Metarhizium robertsii (M. robertsii) as a model to explore the evolution of its dual roles as an entomopathogen and endophyte by examining phenotypic and genomic differences among eight closely related strains. The study found that early diverged strains, characterized by slow germination on insect cuticles, low virulence, and extensive sporulation, exhibit a biotrophic lifestyle, systemically colonizing living hosts. In contrast, recently diverged strains exhibited rapid germination, high virulence, and reduced sporulation, indicating a shift towards a necrotrophic lifestyle. The study highlighted the influence of host immune responses in shaping M. robertsii-insect interactions, and showed that strong insect virulence correlated with better colonization of plant roots. Comparative genomics revealed that recently diverged strains expanded a small number of gene families related to gene expression as well as carbohydrate-degrading enzymes and proteases enhancing metabolic capabilities, insect virulence, and endophytic potential. Some early diverged strains exhibited high Repeat-Induced Point mutation activity, suggesting cryptic sexual reproduction in their evolutionary past. Overall, M. robertsii strains maintained a conserved genome with similar protein family sizes, with differences in gene expression patterns driving their varied lifestyles. This research provides new insights into M. robertsii’s recent co-evolution with plants and insects, highlighting the importance of understanding the ecological and evolutionary dynamics of these interactions for optimizing its use in sustainable agriculture.Item Physiological dynamics of injury and regeneration in the clonal freshwater annelid Pristina leidyi(2022) Rennolds, Corey William; Bely, Alexandra E; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The threat that mechanical injury poses to homeostasis and survival has spurred the evolution of diverse processes to mitigate these effects. The most dramatic of these is regeneration, a process that restores the form and function of lost body parts. The apparent benefits of regeneration may come at considerable cost, however, and these may substantially diminish regeneration’s adaptive value in certain contexts, potentially contributing to evolutionary losses of regeneration. The costs and benefits of regeneration are poorly understood in most animals, precluding more than speculation of the evolutionary drivers of regeneration. Naids are a group of small, clonally reproducing freshwater annelids that feature great diversity of regenerative ability and are well suited to experimental studies. I used the species Pristina leidyi to determine how injury and regeneration affect organismal function and fitness, integrating physiological and molecular approaches. I first investigated how injury and regeneration differentially affect an individual’s ability to tolerate environmental stress, an ecologically relevant and energetically demanding task. I found that stress tolerance is reduced by regeneration in a stressor- and tissue-specific manner while, unexpectedly, tolerance is temporarily improved shortly after injury. These effects are unrelated to whole-organism metabolic rate, which surprisingly does not differ between early and late injury recovery. Using 3’ TagSeq, I found that, while injury and heat stress elicit largely distinct responses, both upregulate certain shared damage control pathways. I then tested whether the physiological cost of regeneration has potential to translate into fitness costs by examining the interaction between regeneration and reproduction, which occurs by asexual fission in this species. By modulating resource availability, I found evidence for an energetic trade-off between regeneration and reproduction that is masked when food is abundant. This tradeoff is manifested through a reduction in per-offspring allocation rather than reproductive rate. Overall, my results demonstrate that injury and regeneration costs are highly context dependent in P. leidyi. More broadly, these findings contrast in key ways from evolutionarily distant animals with very different life history traits, illustrating the importance of investigating the physiological mechanisms that may mediate selection on regeneration in diverse lineages.Item Anatomical and Physiological Characterization of the Turtle Brain Stem Auditory Circuit(2014) Willis, Katie Leann; Carr, Catherine E; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The goal of this dissertation is to add to understanding of the evolution of hearing by studying the testudine taxon. This dissertation focuses on central auditory processing in the context of evolution. The experiments described are designed to give insight into how binaural hearing evolved. Follow the findings of Christensen-Dalsgaard and colleagues (2012) that an amphibious turtle had lower hearing thresholds under water than in air and that this difference is conferred by resonance of the middle ear cavity, I examined middle ear cavities across families of Testudines. I found that middle ear cavity structure and function is shared by all testudines (Willis, et al., 2013). Modern neuroanatomical tract tracing techniques were used to understand the connections among the auditory nuclei in the brain stem of the turtle. Turtles have brain stem nuclei that are connected in the same pattern as the other reptiles, including birds. These nuclei are nucleus angularis, nucleus magnocellularis, nucleus laminaris, superior olive, and torus semicircularis. Details of neuron structure were also examined and quantified. Finally, I developed an isolated head preparation that enables in vivo-like physiological recording. As proof of principle, neurons were characterized by best frequency response, threshold, phase locking. Additionally, binaurally responsive neurons were found, which have a range of interaural time difference sensitivity responses. Although the evolutionary position of testudines is not yet resolved, it is most likely that testudines share their most recent common ancestor with the archosaurs. I hypothesize that testudines likely reflect the ancestral condition of auditory processing for the archosaur clade. All experiments described in this dissertation were performed according to the guidelines approved by the Marine Biological Laboratory (Woods Hole, MA, USA), the University of Maryland Institutional Animal Care and Use Committees (IACUC) and the Danish National Animal Experimentation Board (Dyreforsøgstilsynet).Item COMPUTATIONAL METHODS IN PROTEIN STRUCTURE, EVOLUTION AND NETWORKS.(2013) Cao, Chen; Moult, John; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The advent of new sequencing technology has resulted in the accumulation of a large amount of information on human DNA variation. In order to make sense of these data in the context of biology and medicine, new methods are needed both for analysis and for integration with other resources. In this work: 1) I studied the distribution pattern of human DNA variants across populations using data from the 1000 genomes project and investigated several evolutionary biology questions from the perspective of population genomics. I found population level support for trends previously observed between species, including selection against deleterious variants, and lower frequency of variants in highly expressed genes and highly connected genes. I was also able to show that the correlation between synonymous and non-synonymous variant levels is a consequence of both mutation prevalence variation across the genome and shared selection pressure. 2) I performed a systematic evaluation of the effectiveness of GWAS (Genome Wide Association Studies) for finding potential drug targets and discovered the method is very ineffective for this purpose. I proposed two reasons to explain this finding, selection against variants in drug targets and the relatively short length of drug target genes. I discovered that GWAS genes and drug targets are closely associated in the biological network, and on that basis, developed a machine learning algorithm to leverage the GWAS results for the identification of potential drug targets, making use of biological network information. As a result, I identified some potential drug repurposing opportunities. 3) I developed a method to increase the number of protein structure models available for interpreting the impact of human non-synonymous variants, important for not only the understanding the mechanisms of genetic disease but also in the study of human protein evolution. The method enables the impact of approximately 40% more missense variants to be reliably modeled. In summary, these three projects demonstrate that value of computational methods in addressing a wide range of problems in protein structure, evolution, and networks.Item Characterization of Multiple Surface Loops in Escherichia coli Biotin Protein Ligase Functions(2012) Adikaram, Poorni Ranmali; Beckett, Dorothy; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Multifunctional proteins utilize several strategies to interact with different partners, resulting in diverse cellular outcomes. Structural, thermodynamic and kinetic features of these proteins influence the switch between functions. The Escherichia coli biotin protein ligase, BirA, is a bifunctional protein essential for biotin homeostasis. It transfers biotin to the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase in its metabolic role or dimerizes and binds the biotin biosynthetic operator as a transcriptional repressor. Each function involves forming a protein-protein interaction, and because a single surface of BirA is used to form both interactions, the two are mutually exclusive. The BirA interaction surface contains several loops, two with highly conserved sequences, and the remaining with variable sequences. In this work the roles of four loops in facilitating BirA function were investigated. Amino acids from surface loops were replaced with alanine to obtain 18 alanine substituted variants. Homodimerization energetics measured using sedimentation equilibrium yielded an 8 kcal/mol range for variants from all loops. Steady-state and stopped-flow kinetic assays yielded 7 of 18 variants that exhibited slower rates than wild-type in biotin transfer to BCCP. The majority of alanine substituted variants are from constant loops. These results indicate that the biotin transfer reaction is mediated primarily through the constant loop and homodimerization is facilitated by all surface loops. The energetics of transcription repression complex assembly, which comprises contributions from dimerization and DNA binding, was assessed using DNaseI footprint titrations. Although variants exhibit a broad range in total assembly energetics, all dimers bind with similar affinities to DNA, implying independence between DNA binding and dimerization domains. The switch between functions was also investigated using inhibition DNaseI footprint titrations. A direct correlation between inhibition of repression complex assembly and rates of BirA-BCCP association was observed, reinforcing a kinetic mechanism for the switch between BirA functions. These studies indicate that multiple surface loops form the structural basis for bifunctionality, and BirA switches between protein-protein interactions through a kinetically controlled mechanism. Elucidation of structural and mechanistic aspects of the BirA functional switch enhances our understanding of how multifunctionality evolves and the mechanism of switching between biological functions.Item Computationally Comparing Biological Networks and Reconstructing Their Evolution(2012) Patro, Robert; Kingsford, Carleton L; Computer Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Biological networks, such as protein-protein interaction, regulatory, or metabolic networks, provide information about biological function, beyond what can be gleaned from sequence alone. Unfortunately, most computational problems associated with these networks are NP-hard. In this dissertation, we develop algorithms to tackle numerous fundamental problems in the study of biological networks. First, we present a system for classifying the binding affinity of peptides to a diverse array of immunoglobulin antibodies. Computational approaches to this problem are integral to virtual screening and modern drug discovery. Our system is based on an ensemble of support vector machines and exhibits state-of-the-art performance. It placed 1st in the 2010 DREAM5 competition. Second, we investigate the problem of biological network alignment. Aligning the biological networks of different species allows for the discovery of shared structures and conserved pathways. We introduce an original procedure for network alignment based on a novel topological node signature. The pairwise global alignments of biological networks produced by our procedure, when evaluated under multiple metrics, are both more accurate and more robust to noise than those of previous work. Next, we explore the problem of ancestral network reconstruction. Knowing the state of ancestral networks allows us to examine how biological pathways have evolved, and how pathways in extant species have diverged from that of their common ancestor. We describe a novel framework for representing the evolutionary histories of biological networks and present efficient algorithms for reconstructing either a single parsimonious evolutionary history, or an ensemble of near-optimal histories. Under multiple models of network evolution, our approaches are effective at inferring the ancestral network interactions. Additionally, the ensemble approach is robust to noisy input, and can be used to impute missing interactions in experimental data. Finally, we introduce a framework, GrowCode, for learning network growth models. While previous work focuses on developing growth models manually, or on procedures for learning parameters for existing models, GrowCode learns fundamentally new growth models that match target networks in a flexible and user-defined way. We show that models learned by GrowCode produce networks whose target properties match those of real-world networks more closely than existing models.Item POST-COPULATORY SEXUAL SELECTION AND GAMETIC ISOLATION IN STALK-EYED FLIES(2011) Rose, Emily G.; Wilkinson, Gerald S; Behavior, Ecology, Evolution and Systematics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Understanding the forces that drive lineage splitting, i.e. speciation, has been a goal of evolutionary research since Darwin but remains poorly understood. Sexual selection is frequently invoked as a possible explanation, but focus is typically placed on precopulatory activities where males compete for access to females or females choose among males. The possibility that postcopulatory sexual selection, a powerful evolutionary force which involves interactions between sperm and the female reproductive tract, may contribute to reproductive isolation has only recently been considered. Using diopsid stalk-eyed flies as a model system, I examine divergence in fertilization systems among closely related populations of a single species (Teleopsis dalmanni), in order to assess whether gametic isolation has the potential to contribute to speciation. In chapter 2, I measure a suite of reproductive and non-reproductive morphological traits in eight closely related populations to determine their relative rates of evolution. I find that reproductive traits have diverged more rapidly than non-reproductive traits and that male and female postcopulatory traits, i.e. sperm length and sperm storage organ dimensions, have coevolved. Chapters 3 and 4 describe experiments aimed at elucidating the importance of gametic isolation among these populations. Chapter 3 is an examination of non-competitive gametic isolating barriers. I performed 275 crosses between four populations and measured mechanisms of non-competitive gametic isolation including sperm transfer, sperm survival, sperm motility and ability of sperm to reach the site of fertilization. I conclude that non-competitive gametic isolation exists among these population pairs and specifically identify the inability of sperm to reach the site of fertilization in between-population crosses as a mechanism of reproductive isolation. Chapter 4 is an investigation of competitive gametic isolation which occurs when sperm of males from different populations compete for fertilization. Using two pairs of populations, I carry out every possible combination of crosses and genotype over 1200 offspring to determine paternity. The results demonstrate that sperm competition further inhibits successful hybridization among these closely related populations. I conclude that postcopulatory sexual selection and gametic isolation have the potential to play an important role in the formation of new species in this system.Item Evolution of sex-biased expression in Caenorhabditis(2011) Thomas, Cristel Gwenola; Haag, Eric S; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Mating systems have a profound impact on genome structure evolution, both indirectly through their effects on population genetics and directly due to the genetic control of reproductive traits. Most extant Caenorhabditis species are gonochoristic (males and females), while the most studied species, C. elegans and C. briggsae, are androdioecious (self-fertile hermaphrodites and males). The latter two species display an overall reduced ability to mate, suggesting that the selective pressure on maintaining efficient mating was weakened as selfing arose. The genes underlying these traits were likely to have been expressed in a sex-biased fashion in the gonochoristic ancestor, and we hypothesized that as selfing emerged their regulation was modified or they were lost altogether. This hypothesis is especially interesting given that selfing species have consistently smaller genome sizes than their gonochoristic relatives. I sought to address whether a disproportionate loss of genes with sex-biased expression accompanies the loss of mating-related traits in Caenorhabditis hermaphrodites. I first examine sex-biased expression in a gonochoristic species, C. remanei, and identify genes with highly sex-biased expression. I find that these genes are more likely to be missing in selfing species than expected by chance. I then select some of these genes based on their phylogenetic conservation patterns in the genus, and characterize them more thoroughly to shed some light on their functions. Through this study I identify a novel male-associated candidate cis-regulatory element. Lastly, I broaden the scope of the study by determining transcriptome wide sex-biased expression patterns in four Caenorhabditis species. I confirm that C.elegans displays a decrease in the proportion of strong female-biased expression, as well as a modification of the expression of genes with male-biased expression both in males and in hermaphrodites, when compared to gonochoristic Caenorhabditis. Taken together, this study illustrates the transcriptomic consequences of a modification of the mating system, and begins to address its effect on genome structure.Item Prediction, evolution and privacy in social and affiliation networks(2011) Zheleva, Elena; Getoor, Lise; Computer Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In the last few years, there has been a growing interest in studying online social and affiliation networks, leading to a new category of inference problems that consider the actor characteristics and their social environments. These problems have a variety of applications, from creating more effective marketing campaigns to designing better personalized services. Predictive statistical models allow learning hidden information automatically in these networks but also bring many privacy concerns. Three of the main challenges that I address in my thesis are understanding 1) how the complex observed and unobserved relationships among actors can help in building better behavior models, and in designing more accurate predictive algorithms, 2) what are the processes that drive the network growth and link formation, and 3) what are the implications of predictive algorithms to the privacy of users who share content online. The majority of previous work in prediction, evolution and privacy in online social networks has concentrated on the single-mode networks which form around user-user links, such as friendship and email communication. However, single-mode networks often co-exist with two-mode affiliation networks in which users are linked to other entities, such as social groups, online content and events. We study the interplay between these two types of networks and show that analyzing these higher-order interactions can reveal dependencies that are difficult to extract from the pair-wise interactions alone. In particular, we present our contributions to the challenging problems of collective classification, link prediction, network evolution, anonymization and preserving privacy in social and affiliation networks. We evaluate our models on real-world data sets from well-known online social networks, such as Flickr, Facebook, Dogster and LiveJournal.Item EVOLUTION, DEVELOPMENT, AND GENETICS OF OPSIN GENE EXPRESSION IN AFRICAN CICHLID FISHES(2011) O'Quin, Kelly E; Carleton, Karen L; Behavior, Ecology, Evolution and Systematics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The molecular genetic mechanisms that underlie phenotypic evolution include mutations within protein-coding, cis-regulatory, and trans-regulatory factors. Although many studies have examined how these mutations individually contribute to phenotypic divergence and the formation of new species, none have examined how they may do so collectively. In this study, I examine how these molecular genetic mutations collectively contribute to the evolution of color vision among African cichlid fishes. I show that phenotypic divergence in cichlid color vision is achieved by mutations affecting the coding sequence and expression of seven opsin genes. After contrasting the roles of these two mechanisms, I use bioinformatic-, association-, and experimental genetic analyses to determine what role mutations in cis- and trans-regulatory DNA play in the evolution of cichlid opsin expression. Specifically, I demonstrate that: (1) Protein-coding mutations primarily affect cichlid opsins sensitive to the ends of the visible light spectrum (SWS1 [ultraviolet-sensitive] and LWS [red-sensitive]). (2) Changes in opsin gene expression contribute to large differences in color vision among closely related species. These analyses also reveal that the expression of the SWS1 and SWS2B opsins have diverged among closely related cichlids in association with foraging preferences and ambient light intensity, suggesting that their expression has evolved due to natural selection. Ancestral state reconstructions reveal that changes in opsin expression have evolved repeatedly among cichlids in Lakes Tanganyika and Malawi; further, I find that this repeated evolution has likely been achieved by repeated changes to cichlid development. (3) Bioinformatic analyses suggest that cichlids have diverged in multiple cis-regulatory sequences surrounding the opsin genes, and association mapping identified three putative single nucleotide polymorphisms upstream of the SWS2A (blue), RH2B (blue-green), and LWS (red) opsins that may contribute to cichlid opsin expression differences in cis. (4) Genetic mapping in experimental crosses suggests that divergence in multiple trans-regulatory factors also contribute to the evolution of SWS2B (violet), RH2A (green), and LWS (red) opsin expression. The contribution of these trans-regulatory factors to the evolution of cichlid opsin expression may outweigh those in cis. These results reveal that multiple molecular genetic mechanisms can contribute to phenotypic evolution among closely related species.
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