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- Genre: Academic theses
- Member of: Theses and Dissertations
Description
Mutation is the source of heritable variation of genotype and phenotype, on which selection may act. Mutation rates describe a fundamental parameter of living things, which influence the rate at which evolution may occur, from viral pathogens to human crops and even to aging cells and the emergence of cancer. An understanding of the variables which impact mutation rates and their estimation is necessary to place mutation rate estimates in their proper contexts. To better understand mutation rate estimates, this research investigates the impact of temperature upon transcription rate error estimates; the impact of growing cells in liquid culture vs. on agar plates; the impact of many in vitro variables upon the estimation of deoxyribonucleic acid (DNA) mutation rates from a single sample; and the mutational hazard induced by expressing clustered regularly interspaced short palindromic repeat (CRISPR) proteins in yeast. This research finds that many of the variables tested did not significantly alter the estimation of mutation rates, strengthening the claims of previous mutation rate estimates across the tree of life by diverse experimental approaches. However, it is clear that sonication is a mutagen of DNA, part of an effort which has reduced the sequencing error rate of circle-seq by over 1,000-fold. This research also demonstrates that growth in liquid culture modestly skews the mutation spectrum of MMR- Escherichia coli, though it does not significantly impact the overall mutation rate. Finally, this research demonstrates a modest mutational hazard of expressing Cas9 and similar CRISPR proteins in yeast cells at an un-targeted genomic locus, though it is possible the indel rate has been increased by an order of magnitude.
ContributorsBaehr, Stephan (Author) / Lynch, Michael (Thesis advisor) / Geiler-Samerotte, Kerry (Committee member) / Mangone, Marco (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2023
Description
Viruses are the most abundant biological entities on Earth, infecting all types of cellular organisms. Yet less than 1% of the virosphere on our planet has been characterized to date. Viruses are both an important driver of bacterial evolution and have significant implications for human health, therefore understanding the relative contributions of various evolutionary forces in shaping their genomic landscapes is of critical importance both mechanistically as well as clinically. In my thesis I use computational genomic approaches to gain novel insights into bacteriophage and human cytomegalovirus evolution. In my first two chapters and associated appendices I characterized the complete genomes of the Cluster P bacteriophage Phegasus and Cluster DR bacteriophage BiggityBass, whose isolation hosts were Mycobacterium smegmatis mc²155 and Gordonia terrae CAG3, respectively. I also determined the bacteriophages' phylogenetic placement and computationally inferred their putative host ranges. For my fourth chapter I assessed the performance of several of these computational host range prediction tools using a dataset of bacteriophages whose host ranges have been experimentally validated. Finally, in my fifth chapter I reviewed the key parameters for developing an evolutionary baseline model of another virus, human cytomegalovirus.
ContributorsHowell, Abigail Ann (Author) / Pfeifer, Susanne P (Thesis advisor) / Jensen, Jeffrey (Committee member) / Snyder-Mackler, Noah (Committee member) / Geiler-Samerotte, Kerry (Committee member) / Arizona State University (Publisher)
Created2023
Description
Lignocellulose, the major structural component of plant biomass, represents arenewable substrate of enormous biotechnological value. Microbial production of
chemicals from lignocellulosic biomass is an attractive alternative to chemical synthesis.
However, to create industrially competitive strains to efficiently convert lignocellulose to
high-value chemicals, current challenges must be addressed. Redox constraints, allosteric
regulation, and transport-related limitations are important bottlenecks limiting the
commercial production of renewable chemicals from lignocellulose. Advances in
metabolic engineering techniques have enabled researchers to engineer microbial strains
that overcome some of these challenges but new approaches that facilitate the
commercial viability of lignocellulose valorization are needed. Biological systems are
complex with a plethora of regulatory systems that must be carefully modulated to
efficiently produce and excrete the desired metabolites. In this work, I explore metabolic
engineering strategies to address some of the biological constraints limiting
bioproduction such as redox, allosteric, and transport constraints to facilitate cost-effective
lignocellulose bioconversion.
ContributorsOnyeabor, Moses Ekenedilichukwu (Author) / Wang, Xuan (Thesis advisor) / Varman, Arul M (Committee member) / Nannenga, Brent (Committee member) / Nielsen, David R (Committee member) / Geiler-Samerotte, Kerry (Committee member) / Arizona State University (Publisher)
Created2023
Description
The current study examines responses of Latinx young adult’s (n=65) perceptions, as youth, of disruptions related to the divorce of their parents. To do this, a sample of Latinx young adults who experienced parental divorce during adolescence were asked to retrospectively assess their experiences surrounding their parents’ divorce and their adherence to Latinx cultural values, ethnic socialization, and ethnic identity. Findings indicated higher levels of parental divorce disruptions experienced by participants. Additionally, association between the perceived disruptions and adherence to Latinx cultural values varied across different domains of disruptions related to the divorce. Families also appeared to engage in ethnic socialization of the youth, as the divorce did not disrupt this process. Clinical implications encourage mental health professionals to provide culturally relevant care and opportunities for ethnic identity exploration for Latinx young adult clients who are from divorced households.
ContributorsCovarrubias, Leonard (Author) / Capielo Rosario, Cristalís (Thesis advisor) / Randall, Ashley (Committee member) / Truong, Nancy (Committee member) / Arizona State University (Publisher)
Created2022
Description
Given the prevalence and severity of dating violence (DV) in our World, uncovering the long-term effects of DV is pivotal. This thesis provides information about how prior DV impacts a survivor’s future relationships. First, understanding the association between prior DV and current relationship satisfaction. Next, suggesting potential moderators between DV and current relationship satisfaction in forms of resilience. Tangible resilience strategies such as seeking therapy and obtaining an order of protection were assessed as potential moderators. As well as one’s attachment style as a predictor of how one overcomes prior DV and impacts current relationship satisfaction. A study was conducted with 218 participants from both the United States and international countries. Prior DV was a predictor of relationship satisfaction, however in the adverse way as predicted. Survivors of prior dating violence reported higher levels of current relationship satisfaction. Tangible resilience and secure attachment style were both significant moderators of the relationship between prior DV and current relationship satisfaction. These results present new ways to face the challenge of overcoming the repercussions of DV for survivors. As well as provide hope and support to all survivors of DV that their past does not have to impact their future.
ContributorsGraham, Kaylyn (Author) / Mickelson, Kristin (Thesis advisor) / Randall, Ashley (Committee member) / Burleson, Mary (Committee member) / Arizona State University (Publisher)
Created2022
Description
Interpersonal communication can facilitate or inhibit positive mental-health outcomes, depending on a large number of factors. This study investigates associations among communication behaviors, social network factors, and a mental health outcome (distress) in frenemy relationships. Frenemy relationships refer to individuals who have negative feelings toward relational partners, but their interactions are typically performed to be seen as positive. In short, individuals conceal their negative feelings toward a partner while maintaining positive interactions. Given this definition and existing literature, deceptive affection and relational aggression were two communication behaviors that are likely to occur in frenemy relationships that are likely to negatively influence mental health. Therefore, this dissertation investigated the extent to which deceptive affection and relational aggression influence distress when communicating with a frenemy. In addition, like other interpersonal relationships, frenemy relationships are embedded in larger social networks which have also been found to influence mental health outcomes, either positively or negatively. Thus, this dissertation also examined how two social network factors – social network awareness of the frenemy relationship and social network liking of the frenemy – influence distress experienced when talking with the frenemy. Two hundred and seventy-nine non-college adults accessed the survey through Amazon’s Mechanical Turk and completed an online survey through Qualtrics. The results of multiple regression analyses indicated a positive association between relational aggression behaviors and distress when communicating with a frenemy. Results also showed that social network liking and social network awareness interact to influence distress. When the social network likes the frenemy, awareness of the frenemy relationship positively is positively related to distress. When the social network dislikes the frenemy, on the other hand, awareness of the relationship makes no difference on distress. Directions for future research include a number of interesting theoretical implications that link the present results to a variety of theoretical notions and concepts.
ContributorsYu, Panfeng (Author) / Mongeau, Paul (Thesis advisor) / Randall, Ashley (Committee member) / Guerrero, Laura (Committee member) / Arizona State University (Publisher)
Created2023
Description
Black individuals and transgender and nonbinary (TNB) populations encounter daily microaggressions that negatively impact their mental health. Identity pride has been shown to moderate this association for Black and TNB populations separately. Unfortunately, research has not examined the impacts of simultaneously experiencing race-based and gender-based microaggressions in populations such as Black nonbinary individuals. Given this, there remains a significant gap in understanding the mental health impacts of racial and gender microaggressions and potential buffers for Black nonbinary individuals. The current study (N = 65) aimed to evaluate the association between intersectional microaggressions (IM) and depression and anxiety in Black nonbinary adults and the potential moderating effects of Black pride and nonbinary pride. A sample of Black nonbinary individuals was obtained from a larger longitudinal study with nonbinary adults. Hierarchical multiple regression analyses were run to examine the association between intersectional microaggressions and mental health outcomes and the interactions of Black pride and nonbinary pride. Results showed that intersectional microaggressions did not significantly predict depression or anxiety. Neither Black nor nonbinary pride were significant moderators of the association between IM and depression. For anxiety, results showed that Black pride was a significant moderator, such that those with higher levels of Black pride showed a stronger association between IM and anxiety. Further research is needed to investigate the impact of Black pride on anxiety and identify additional protective factors outside of pride for Black nonbinary individuals.
ContributorsHolman, Mel (Author) / Matsuno, Em (Thesis advisor) / Randall, Ashley (Committee member) / Capielo Rosario, Cristalís (Committee member) / Arizona State University (Publisher)
Created2023
Description
Phenotypic evolution is of great significance within biology, as it is the culmination of the influence of key evolutionary factors on the expression of genotypes. Deeper studies of the fundamental components, such as fitness effects of mutations and genetic variance within a population, allow one to predict the evolutionary trajectory of phenotypic evolution. In this regard, how much the change in mutational variance and the ongoing natural selection influence the rate of phenotypic evolution has yet to be fully understood. Therefore, this study measured mutational variances and the increasing rate of genetic variance during the experimental evolution of Escherichia coli populations, focusing on two growth-related traits, the populational maximum growth rate and carrying capacity. Mutational variances were measured by mutation-accumulation experiments, which allowed for the analysis of the effects of spontaneous mutations on growth-related traits in the absence of selection. This analysis revealed that some evolved populations developed a higher mutational variance for growth-related traits. Further investigation showed that most evolved populations have also developed a greater mutational effect, which could explain the increase in mutational variance. Finally, the genetic variances for most evolved populations are lower than expected in the absence of selection, and the involvement of either stabilizing or directional selection is evident. Future experiments with a larger sample size of experimentally evolved populations, as well as more intermediate timepoints during experimental evolution, may provide further insight regarding the complexities of the evolutionary outcomes of these traits.
ContributorsGonzales, Jadon (Author) / Lynch, Michael (Thesis advisor) / Geiler-Samerotte, Kerry (Committee member) / Ho, Wei-Chin (Committee member) / Arizona State University (Publisher)
Created2023
Description
Protein misfolding is a problem faced by all organisms, but the reasons behind misfolded protein toxicity are largely unknown. It is difficult to pinpoint one exact mechanism as the effects of misfolded proteins can be widespread and variable between cells. To better understand their impacts, here I explore the consequences of misfolded proteins and if they affect all cells equally or affect some cells more than others. To investigate cell subpopulations, I built and optimized a cutting-edge single-cell RNA sequencing platform (scRNAseq) for yeast. By using scRNAseq, I can study the expression variability of many genes (i.e. how the transcriptomes of single cells differ from one another). To induce misfolding and study how single cells deal with this stress, I use engineered strains with varying degrees of an orthogonal misfolded protein. When I computationally cluster the cells expressing misfolded proteins by their sequenced transcriptomes, I see more cells with the severely misfolded protein in subpopulations undergoing canonical stress responses. For example, I see these cells tend to overexpress chaperones, and upregulate mitochondrial biogenesis and transmembrane transport. Both of these are hallmarks of the “Generalized” or “Environmental Stress Response” (ESR) in yeast. Interestingly, I do not see all components of the ESR upregulated in all cells, which may suggest that the massive transcriptional changes characteristic of the ESR are an artifact of having defined the ESR in bulk studies. Instead, I see some cells activate chaperones, while others activate respiration in response to stress. Another intriguing finding is that growth supporting proteins, such as ribosomes, have particularly heterogeneous expression levels in cells expressing misfolded proteins. This suggests that these cells potentially reallocate their metabolic functions at the expense of growth but not all cells respond the same. In sum, by using my novel single-cell approach, I have gleaned new insights about how cells respond to stress. which can help me better understand diseased cells. These results also teach how cells contend with mutation, which commonly causes protein misfolding and is the raw material of evolution. My results are the first to explore single-cell transcriptional responses to protein misfolding and suggest that the toxicity from misfolded proteins may affect some cells’ transcriptomes differently than others.
ContributorsEder, Rachel (Author) / Geiler-Samerotte, Kerry (Thesis advisor) / Brettner, Leandra (Committee member) / Wideman, Jeremy (Committee member) / Arizona State University (Publisher)
Created2023
Description
Transgender and nonbinary (TNB) people experience elevated rates of post-traumatic stress disorder (PTSD) due to transphobic violence, discrimination, microaggressions, and minority stress. Oppression against TNB people could also contribute to complex post-traumatic stress disorder (c-PTSD) symptoms, which arises due to exposure to prolonged and repeated trauma from a state of subordination. Nonbinary people in particular experience unique chronic minority stressors (e.g., misgendering, interpersonal invalidation) because of the assumption that gender is inherently binary. These chronic minority stressors threaten nonbinary people’s psychological and interpersonal senses of safety. This study aims to examine how misgendering and invalidation can predict PTSD and c-PTSD symptoms among nonbinary people and whether this association is moderated by pride and community connectedness. Cross-sectional data from 611 nonbinary people were analyzed using hierarchical linear regressions. Misgendering and invalidation were found to be significant predictors of PTSD and c-PTSD symptoms. However, pride and community connectedness were not significant moderators of these associations. Findings from this study contribute to the conceptualizations of traumatic stress among nonbinary people and provide considerations for more affirming trauma-informed care. Future research should explore how additional resilience factors may promote resilience and healing for nonbinary people coping with trauma.
ContributorsColson, Alex (Author) / Matsuno, Em (Thesis advisor) / Randall, Ashley (Committee member) / Barr, Sebastian (Committee member) / Arizona State University (Publisher)
Created2023