Matching Items (40)
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- All Subjects: Evolution
- Creators: School of Life Sciences
- Status: Published
Description
Many factors are at play within the genome of an organism, contributing to much of the diversity and variation across the tree of life. While the genome is generally encoded by four nucleotides, A, C, T, and G, this code can be expanded. One particular mechanism that we examine in this thesis is modification of bases—more specifically, methylation of Adenine (m6A) within the GATC motif of Escherichia coli. These methylated adenines are especially important in a process called methyl-directed mismatch repair (MMR), a pathway responsible for repairing errors in the DNA sequence produced by replication. In this pathway, methylated adenines identify the parent strand and direct the repair proteins to correct the erroneous base in the daughter strand. While the primary role of methylated adenines at GATC sites is to direct the MMR pathway, this methylation has also been found to affect other processes, such as gene expression, the activity of transposable elements, and the timing of DNA replication. However, in the absence of MMR, the ability of these other processes to maintain adenine methylation and its targets is unknown.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
ContributorsBoyer, Gwyneth (Author) / Lynch, Michael (Thesis director) / Behringer, Megan (Committee member) / Geiler-Samerotte, Kerry (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Many bacteria actively import environmental DNA and incorporate it into their genomes. This behavior, referred to as transformation, has been described in many species from diverse taxonomic backgrounds. Transformation is expected to carry some selective advantages similar to those postulated for meiotic sex in eukaryotes. However, the accumulation of loss-of-function alleles at transformation loci and an increased mutational load from recombining with DNA from dead cells create additional costs to transformation. These costs have been shown to outweigh many of the benefits of recombination under a variety of likely parameters. We investigate an additional proposed benefit of sexual recombination, the Red Queen hypothesis, as it relates to bacterial transformation. Here we describe a computational model showing that host-pathogen coevolution may provide a large selective benefit to transformation and allow transforming cells to invade an environment dominated by otherwise equal non-transformers. Furthermore, we observe that host-pathogen dynamics cause the selection pressure on transformation to vary extensively in time, explaining the tight regulation and wide variety of rates observed in naturally competent bacteria. Host-pathogen dynamics may explain the evolution and maintenance of natural competence despite its associated costs.
ContributorsPalmer, Nathan David (Author) / Cartwright, Reed (Thesis director) / Wang, Xuan (Committee member) / Sievert, Chris (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
We examined the evolutionary morphological responses of Drosophila melanogaster that had evolved at constant cold (16°), constant hot (25°C), and fluctuating (16° and 25°C). Flies that were exposed to the constant low mean temperature developed larger thorax, wing, and cell sizes than those exposed to constant high mean temperatures. Males and females both responded similarly to thermal treatments in average wing and cell size. The resulting cell area for a given wing size in thermal fluctuating populations remains unclear and remains a subject for future research.
ContributorsAdrian, Gregory John (Author) / Angilletta, Michael (Thesis director) / Harrison, Jon (Committee member) / Rusch, Travis (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Since its discovery in 1524, many people have characterized the vermiform appendix. Charles Darwin considered the human appendix to be a vestige and a useless structure. Others at the time opposed this hypothesis. However, Darwin's hypothesis became prevalent one until recently when there became a renewed interest in the appendix because of advancements in microscopes, knowledge of the immune system, and phylogenetics. In this review, I will argue that the vermiform appendix, although still not completely understood, has important functions. First, I will give the anatomy of the appendix. I will discuss the comparative anatomy between different animals and also primates. I will address the effects of appendicitis and appendectomy. I will give background on vestigial structures and will discuss if the appendix is a vestige. Following, I will review the evolution of the appendix. Finally, I will argue that the function of the appendix is as an immune organ, including discussion of gut-associated lymphoid tissue (GALT), development of lymphoid follicles in GALT and their comparison within different organs, Immunoglobulin A (IgA) function in the gut, biofilms as evidence that the appendix is a safe-house for beneficial bacteria, re-inoculation of the bowel, and protection against recurring infection. I will conclude with future studies that should be conducted to further our understanding of the vermiform appendix.
ContributorsPrestwich, Shelby Elizabeth (Author) / Cartwright, Reed (Thesis director) / Lynch, John (Committee member) / Furstenau, Tara (Committee member) / School of Geographical Sciences and Urban Planning (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The Cannabis plant has historical roots with human beings. The plant produces compounds called cannabinoids, which are responsible for the physiological affects of Cannabis and make it a research candidate for medicinal use. Analysis of the plant and its components will help build a better database that could be used to develop a complete roster of medicinal benefits. Research regarding the cellular protein receptors that bind the cannabinoids may not only help provide reasons explaining why the Cannabis plant could be medicinally relevant, but will also help explain how the receptors originated. The receptors may have been present in organisms before the present day Cannabis plant. So why would there be receptors that bind to cannabinoids? Searching for an endocannabinoid system could help explain the purpose of the cannabinoid receptors and their current structures in humans. Using genetic technologies we are able to take a closer look into the evolutionary history of cannabinoids and the receptors that bind them.
ContributorsSalasnek, Reed Samuel (Author) / Capco, David (Thesis director) / Mangone, Marco (Committee member) / Stump, Edmund (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The evolution of blindness in cave animals has been heavily studied; however, little research has been done on the interaction of migration and drift on the development of blindness in these populations. In this study, a model is used to compare the effect that genetic drift has on the fixation of a blindness allele for varying amounts of migration and selection. For populations where the initial frequency is quite low, genetic drift plays a much larger role in the fixation of blindness than populations where the initial frequency is high. In populations where the initial frequency is high, genetic drift plays almost no role in fixation. Our results suggest that migration plays a greater role in the fate of the blindness allele than selection.
ContributorsMerry, Alexandra Leigh (Author) / Cartwright, Reed (Thesis director) / Rosenberg, Michael (Committee member) / Schwartz, Rachel (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
This creative thesis project aimed to create career development resources that School of Life Sciences majors could use to enhance their college experience, expand the breadth of relevant career options for School of Life Sciences majors, and confront and divert career problems through the implementation of these career development resources. Students encounter career problems when their intention and action diverge. These career problems may cause a student to stop their pursuit of a given career, change majors, or even stop schooling completely. It is the objective of this project to help resolve these career problems by introducing a career development resource flyer that educates the student about a given career, provides coursework to guide a student towards this career path, familiarize students with extracurricular efforts necessary for this position, propose valuable resources that the student can utilize to learn more about the career, and offer a question and answer portion for further career and professional understanding. In order to create these career development resource flyers a variety of professionals, both with and without relationships with Arizona State University were contacted and interviewed. The answers gathered from these interviews were then utilized to create the career flyers. The project was successful in creating five distinct career development resource flyers, as well as a blank template with instructions to be used in the future by the School of Life Sciences. The career development resource flyers will be utilized by the School of Life Sciences advising staff for future exploratory majors, but is not limited to just these students. Aspirations are set to create an expansive reservoir of these resources for future generations of students to access in hopes that they will be better suited to find a career path that they are passionate about and be better prepared to attain.
ContributorsGallegos, Darius Sloan (Author) / Wilson Sayres, Melissa (Thesis director) / Downing, Virginia (Committee member) / DeNardo, Dale (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born therefore requires the ability to breakdown the lactose in the milk to ensure its proper digestion (Segurel & Bon, 2017). Generally, humans lose the expression of lactase after weaning, which prevents them being able to breakdown lactose from dairy (Flatz, 1987).
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.
ContributorsJobe, Ndey Bassin (Author) / Wilson Sayres, Melissa (Thesis director) / Paaijmans, Krijn (Committee member) / Taravella, Angela (Committee member) / School of Earth and Space Exploration (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
While specific resistance mechanisms to targeted inhibitors in BRAF-mutant cutaneous melanoma have been identified, surprisingly little is known about the rate at which resistance develops under different treatment options. There is increasing evidence that resistance arises from pre-existing clones rather than from de novo mutations, but there remains the need for a better understanding of how different drugs affect the fitness of clones within a tumor population and promote or delay the emergence of resistance. To this end, we have developed an assay that defines the in vitro rate of adaptation by analyzing the progressive change in sensitivity of a melanoma cell line to different treatments. We performed a proof-of-theory experiment based on the hypothesis that drugs that cause cell death (cytotoxic) impose a higher selection pressure for drug-resistant clones than drugs that cause cell-cycle arrest (cytostatic drugs), thereby resulting in a faster rate of adaptation. We tested this hypothesis by continuously treating the BRAFV600E melanoma cell line A375 with the cytotoxic MEK inhibitor E6201 and the cytostatic MEK inhibitor trametinib, both of which are known to be effective in the setting of constitutive oncogenic signaling driven by the BRAF mutation. While the identification of confounding factors prevented the direct comparison between E6201-treated and trametinib-treated cells, we observed that E6201-treated cells demonstrate decreased drug sensitivity compared to vehicle-treated cells as early as 18 days after treatment begins. We were able to quantify this rate of divergence at 2.6% per passage by measuring the increase over time in average viability difference between drug-treated and vehicle-treated cells within a DDR analysis. We argue that this value correlates to the rate of adaptation. Furthermore, this study includes efforts to establish a barcoded cell line to allow for individual clonal tracking and efforts to identify synergistic and antagonist drug combinations for use in future experiments. Ultimately, we describe here a novel system capable of quantifying adaptation rate in cancer cells undergoing treatment, and we anticipate that this assay will prove helpful in identifying treatment options that circumvent or delay resistance through future hypothesis-driven experiments.
ContributorsDe Luca, Valerie Jean (Author) / Wilson Sayres, Melissa (Thesis director) / Trent, Jeff (Committee member) / Hendricks, William (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Abstract The BIO 189 Life Sciences Career Paths course is a seminar course that is intended to acclimate incoming freshmen into the School of Life Sciences (SOLS). While there are instructors who organize and present in the class, upper division undergraduate students are primarily responsible for facilitating lectures and discussions and mentoring the freshmen. Prior research has demonstrated that the mentor-mentee relationship is a very important predictor of success and retention within all university first-year programs. While past studies focused on the student mentor-mentee relationships, there is limited research that measures student satisfaction within freshmen seminar courses, especially in areas of science, technology, engineering, and mathematics (STEM). The purpose of this project is to survey students about their perception of the BIO 189 course. The effort of the project is on pre-health students, as they initiate their undergraduate careers and attempt to achieve acceptance into professional school four years later. Analysis of Likert scale surveys distributed to 561 freshmen revealed that students with an emphasis on "medicine" in their majors preferred a BIO 189 course geared to pre-health interests whereas students seeking an emphasis on research (ecology and cell biology/genetics) sought a BIO 189 course focused on internship and employment opportunities. Assessment of the mentor-mentee relationship revealed that students (n = 561) preferred one-on-one meetings with mentors outside of class (44%) compared to those who preferred interaction in class (30%). A sizable 61.68% of students (n = 548) were most concerned with attaining favorable GPAs, highlighting strong emphasis on academic performance. Overall, 61% of respondents (n = 561) expressed satisfaction with SOLS resources and involvement opportunities, which was hypothesized. These results give substantial insight into the efficacy of a first-year success seminar-mentoring program for college freshmen in STEM.
ContributorsMaalouf, Nicholas Elie (Author) / Haydel, Shelley (Thesis director) / Harrell, Carita (Committee member) / Capco, David (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12