Matching Items (6)
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- All Subjects: Genetics
- Genre: Academic theses
- Creators: Laubichler, Manfred
- Member of: ASU Electronic Theses and Dissertations
- Resource Type: Text
Description
Malaria is a vector-borne parasitic disease affecting tropical and subtropical regions. Regardless control efforts, malaria incidence is still incredible high with 219 million clinical cases and an estimated 660,000 related deaths (WHO, 2012). In this project, different population genetic approaches were explored to characterize parasite populations. The goal was to create a framework that considered temporal and spatial changes of Plasmodium populations in malaria surveillance. This is critical in a vector borne disease in areas of low transmission where there is not accurate information of when and where a patient was infected. In this study, fragment analysis data and single nucleotide polymorphism (SNPs) from South American samples were used to characterize Plasmodium population structure, patterns of migration and gene flow, and discuss approaches to differentiate reinfection vs. recrudescence cases in clinical trials. A Bayesian approach was also applied to analyze the Plasmodium population history by inferring genealogies using microsatellites data. Specifically, fluctuations in the parasite population and the age of different parasite lineages were evaluated through time in order to relate them with the malaria control plan in force. These studies are important to understand the turnover or persistence of "clones" circulating in a specific area through time and consider them in drug efficacy studies. Moreover, this methodology is useful for assessing changes in malaria transmission and for more efficiently manage resources to deploy control measures in locations that act as parasite "sources" for other regions. Overall, these results stress the importance of monitoring malaria demographic changes when assessing the success of elimination programs in areas of low transmission.
ContributorsChenet, Stella M (Author) / Escalante, Ananias A (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Rosenberg, Michael (Committee member) / Taylor, Jesse E (Committee member) / Arizona State University (Publisher)
Created2014
Description
Gene-centric theories of evolution by natural selection have been popularized and remain generally accepted in both scientific and public paradigms. While gene-centrism is certainly parsimonious, its explanations fall short of describing two patterns of evolutionary and social phenomena: the evolution of sex and the evolution of social altruism. I review and analyze current theories on the evolution of sex. I then introduce the conflict presented to gene-centric evolution by social phenomena such as altruism and caste sterility in eusocial insects. I review gene-centric models of inclusive fitness and kin selection proposed by Hamilton and Maynard Smith. Based their assumptions, that relatedness should be equal between sterile workers and reproductives, I present several empirical examples that conflict with their models. Following that, I introduce a unique system of genetic caste determination (GCD) observed in hybrid populations of two sister-species of seed harvester ants, Pogonomyrmex rugosus and Pogonomyrmex barbatus. I review the evidence for GCD in those species, followed by a critique of the current gene-centric models used to explain it. In chapter two I present my own theoretical model that is both simple and extricable in nature to explain the origin, evolution, and maintenance of GCD in Pogonomyrmex. Furthermore, I use that model to fill in the gaps left behind by the contributing authors of the other GCD models. As both populations in my study system formed from inter-specific hybridization, I review modern discussions of heterosis (also called hybrid vigor) and use those to help explain the ecological competitiveness of GCD. I empirically address the inbreeding depression the lineages of GCD must overcome in order to remain ecologically stable, demonstrating that as a result of their unique system of caste determination, GCD lineages have elevated recombination frequencies. I summarize and conclude with an argument for why GCD evolved under selective mechanisms which cannot be considered gene-centric, providing evidence that natural selection can effectively operate on non-heritable genotypes appearing in groups and other social contexts.
ContributorsJacobson, Neal (Author) / Gadau, Juergen (Thesis advisor) / Laubichler, Manfred (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2012
Description
In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression which prevents deleterious side effects from having too much or too little expression of genes on sex chromsomes. The green anole is part of a group of species that recently underwent an adaptive radiation. The green anole has XX/XY sex determination, but the content of the X chromosome and its evolution have not been described. Given its status as a model species, better understanding the green anole genome could reveal insights into other species. Genomic analyses are crucial for a comprehensive picture of sex chromosome differentiation and dosage compensation, in addition to understanding speciation.
In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.
In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.
In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.
In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.
ContributorsRupp, Shawn Michael (Author) / Wilson Sayres, Melissa A (Thesis advisor) / Kusumi, Kenro (Committee member) / DeNardo, Dale (Committee member) / Arizona State University (Publisher)
Created2016
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
How is knowledge created at the intersections between basic science, biotechnology, and industry? Gene drives are an interesting example, as they combine a long-standing interest with a recent technological breakthrough and a new set of commercial applications. Gene drives are genes engineered such that they are preferentially inherited at a frequency greater than the typical Mendelian fifty percent ratio. During the historical and conceptual evolution of gene drives beginning in the 1960s, there have been many innovations and publications. Along with that, gene drive science developed considerable public attention, explosion of new scientists, and variation in the way the topic is discussed. It is now time to look at this new organization of science using a systematic approach to characterize the system that has enabled knowledge to grow in this scientific field. This project breaks new ground in how knowledge advances in genetic engineering science, and how scientists understand what a “gene drive” is through analysis of language, communities, and other social factors. In effect, this research will advance multiple fields and enable a deeper understanding of knowledge and complexity. This project documents patterns of publication, collaborative relationships, linguistic variation, innovation, and knowledge expansion. The results of computational analysis provide an in-depth and complete characterization of the structure, dynamics, and evolution of scientific knowledge found in the gene drive technology. Further, time series analysis of the multiple layers of discourse enabled a diachronic connective mapping of collaborative relationships and tracked linguistic variation and change, highlighting where ambiguous language may appear, improving and creating more cohesive scientific language.
Overall, depicting the structure, dynamics, and evolution of scientific knowledge during a novel eruption of scientific complexity can shed light on the factors that can lead to: (1) improved scientific communication, (2) reduction of scientific progress, (3) new knowledge, and (4) novel collaborative relationships. Therefore, characterizing the current technological, methodological, and social contexts that can influence scientific knowledge.
ContributorsOToole, Cody Lane (Author) / Laubichler, Manfred (Thesis advisor) / Collins, James P (Committee member) / Simeone, Michael (Committee member) / Evans, James (Committee member) / Arizona State University (Publisher)
Created2021
Description
Transgenic experiments in Drosophila have proven to be a useful tool aiding in the
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
ContributorsStinchfield, Michael J (Author) / Newfeld, Stuart J (Thesis advisor) / Capco, David (Committee member) / Laubichler, Manfred (Committee member) / Arizona State University (Publisher)
Created2019