The morphological characteristics of organisms are intricately linked to their ecological features. As a result, species with similar ecological niches may exhibit shared morphological traits due to convergent evolution. Some genomic features could be relevant to influencing the occurrence of…
The morphological characteristics of organisms are intricately linked to their ecological features. As a result, species with similar ecological niches may exhibit shared morphological traits due to convergent evolution. Some genomic features could be relevant to influencing the occurrence of convergence evolution. Anoles, with over 400 species, are an excellent model for studying this process. Within Anolis, groups of species that have evolved similar morphological traits and ecological adaptations in response to specific environmental niches are described as ecomorphs. One ecomorph, the crown-giant anoles, has independently evolved large body sizes and adapted to arboreal habitats, predominantly occupying the upper canopy layer of forests. The objective of this study was to explore the convergent evolution of morphological traits in crown giant anoles, by comparing the osteological traits of two crown giants, Anolis frenatus, and A. equestris, to four non-crown giant species from different ecomorphs, A. auratus, A. carolinensis, A. biporcatus, and A. sagrei. The analysis indicated an absence of convergence in most morphological traits except for body size (SVL). Additionally, this study explored the potential role of transposable elements (TEs) as a genomic feature shaping the morphological diversity of crown giant anoles. The genes located within TE-rich regions on the genome were identified across selected Anolis species. An enrichment of genes associated with regulation and developmental processes was detected in regions with high TE abundance for all analyzed species, but not exclusive to crown giants. The results suggest that crown giants seem to only converge in their substantial body size and that the variability in other morphological characteristics could be attributed to some other ecological features or the phylogenetic relationships of each species. Moreover, TEs may play a role in facilitating morphological evolution and adaptability in all Anolis species, as they could influence gene expression and regulatory pathways. This highlights the need for further investigation into the genomic mechanisms determining convergent evolution.
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The ecological niche of a species can shift due to changing environmental conditions and lead to the species to undergo selective pressures to adapt to them. Ecological niche models are used to predict a species’ distribution based on its ecological…
The ecological niche of a species can shift due to changing environmental conditions and lead to the species to undergo selective pressures to adapt to them. Ecological niche models are used to predict a species’ distribution based on its ecological niche. Ecological niche models can be integrated with a geographic information system to predict a species’ geographic distribution based on environmental variables. In this project, two reptile species that inhabit wide and variable geographic ranges, Uta stansburiana and Gopherus berlandieri, had their ecological niches predicted and mapped based off population data and climactic data. These ecological niche maps were then compared to sample populations of each species to infer and predict whether certain populations of each species were possibly under increased selective pressures. Based off these maps and comparisons, this study infers that the two species differ in which environmental variables are the most relevant to their suitability. This study also predicts that populations of U. stansburiana experiencing extremes in their most relevant values for temperature and precipitation could be under greater selective pressures, while populations of G. berlandieri experiencing lower values for their relevant temperature and precipitation variables could be under greater selective pressures. Furthermore, it can be inferred from this study that differences in these variables across each species’ range could be influencing genetic variation among their populations, in line with previous studies. Further genomic study of each species can be used to test these inferences.
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Structural Equation Modeling (SEM) is a multivariate analysis methodology that could potentially be utilized to examine the barrier effect that river systems have on genetic differentiation. In this project, river systems are split into the variables of Daily Average Discharge,…
Structural Equation Modeling (SEM) is a multivariate analysis methodology that could potentially be utilized to examine the barrier effect that river systems have on genetic differentiation. In this project, river systems are split into the variables of Daily Average Discharge, Average River Width, and Seasonality measurements and regressed onto the genetic differentiation, measured as Fst. This data was collected from the USGS database (U.S. Geological Survey, 2020), sequencing files from differing literature, or Google Earth measurements. Different Structural Equation Modeling models are used to model different system structures as well as compare it to more traditional methodologies like Generalized Linear Modeling and Generalized Linear Mixed Modeling. Ultimately results were limited by the small sample size, however, interesting patterns still emerged from the models. The SE models indicate that Discharge plays a primary role in the genetic differentiation of adjacent river populations. In addition to this, the results demonstrate how quantification of indirect effects, particularly those relating to discharge, give more informative interpretations than traditional multivariate statistics alone. These findings prompt further investigations into this potential methodology.
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Our bodies are constantly fighting off viral pathogens both with our external barriers such as skin as well as internally through the immune system. Mucin genes specifically Muc5AC and Muc5B help assist in this process by activating both bacterial and…
Our bodies are constantly fighting off viral pathogens both with our external barriers such as skin as well as internally through the immune system. Mucin genes specifically Muc5AC and Muc5B help assist in this process by activating both bacterial and mucus pathogenesis. Their gene expression is correlated with temperature meaning that in warmer temperatures they have decreased expression. Developing a better understanding of their functionality as well as their expression can help species that are in danger of becoming extinct.
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Heat shock factors (HSFs) are transcriptional regulators that play a crucial role in the cellular response to environmental stress, particularly heat stress. Understanding the evolution of HSFs can provide insights into the adaptation of organisms to their changing environments. This…
Heat shock factors (HSFs) are transcriptional regulators that play a crucial role in the cellular response to environmental stress, particularly heat stress. Understanding the evolution of HSFs can provide insights into the adaptation of organisms to their changing environments. This project explored the evolution of HSFs within tetrapods, a group of animals that includes amphibians, reptiles, turtles, and mammals. Through an analysis of the available genomic data and subsequent genomic methodologies, HSFs have undergone significant changes throughout tetrapod evolution, as evidenced by loss events observed in protein sequences of the species under examination. Moreover, several conserved and divergent regions within HSF proteins were identified, which may reflect functional differences between HSFs in different tetrapod lineages. Our findings suggest that the evolution of HSFs has contributed to the adaptation of tetrapods to their diverse environments and that further research on the functional and regulatory differences between HSFs may provide a better understanding of how organisms cope with stress in heat-stressed environments.
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Skeletal muscle can intrinsically repair itself in response to injury. This repair process has been shown to be mediated through signaling of the innate immune system. The immune response caused during repair helps to clear away debris in damage and…
Skeletal muscle can intrinsically repair itself in response to injury. This repair process has been shown to be mediated through signaling of the innate immune system. The immune response caused during repair helps to clear away debris in damage and promotes the activation and proliferation of muscle stem cells (MuSCs) that will repair the damage muscle. Dysregulation of this inflammation leads to fibrosis and decreased efficacy of the repair process. Despite the requirement of inflammatory signaling during muscle repair, muscle’s contribution during inflammation as only recently started to be explored. The objective of this dissertation is to assess the contribution of muscle in the early inflammatory response during repair as well attempting to modulate this inflammation during disease to ameliorate disease pathology in a model of Duchenne’s muscular dystrophy. I tested the hypotheses that 1) muscle is an active participant in the early inflammatory response, 2) the transcription factor Mohawk (Mkx) is a regulator of the early inflammatory response and, 3) If this inflammation can be modulated with a virally derived serine protease inhibitor in a model of muscle disrepair and chronic inflammation. I found that muscle is actively participating in the establishment early inflammation in repair through the production of chemokines used to promote infiltration of immune cells. As well as the identification of a new muscle subtype that produces more chemokines compared to the average MuSC and upregulated genes in the Interferon signaling pathway. I also discovered that presence of this muscle subtype is linked to the expression of Mkx. In Mkx null mice this population is not present, and these cells are deficient in chemokine expression compared to WT mice. I subsequently found that, using the myxomavirus derived serine protease inhibitor, Serp-1 I was able to modulate the chronic inflammation that is common in those affected with Duchenne’s muscular dystrophy (DMD) utilizing a high-fidelity mouse model of the disease. The result of this dissertation provides an expanded role for muscle in inflammation and gives a potential new class of therapeutics to be used in disease associated with chronic inflammation.
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Wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to restore the skin's barrier function post-injury. Proteolytic enzymes, in particular matrix metalloproteinases (MMPs), contribute to all phases of the healing…
Wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to restore the skin's barrier function post-injury. Proteolytic enzymes, in particular matrix metalloproteinases (MMPs), contribute to all phases of the healing process by regulating immune cell influx, clearing out the extracellular matrix (ECM), and remodeling scar tissue. As a result of these various functions in the healing of skin wounds, uncontrolled activities of MMPs are associated with impaired wound healing. The MMP gene family consists of a highly conserved set of genes. Deleterious mutations in MMP genes cause developmental phenotypes that affect the heart, skeleton, and immune system response.
The availability of contiguous draft genomes of non-model organisms enables the study of gene families through analysis of synteny and sequence identity. My project is aimed at conducting a comparative genomic analysis of the MMP gene family from the genomes of 29 tetrapod species—with an emphasis on reptiles. Results regarding the similarities and differences among MMP protein sequences can be further investigated to shed light on the causes which give rise to various adaptive mutations for specific species groups.
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Structural Equation Modeling was utilized to examine the relationships between river characteristics and genetic differentiation. These river characteristics were river width, annual discharge, and seasonality. This methodology showed great reliability and also resulted in significant insight in how to model…
Structural Equation Modeling was utilized to examine the relationships between river characteristics and genetic differentiation. These river characteristics were river width, annual discharge, and seasonality. This methodology showed great reliability and also resulted in significant insight in how to model a network of Earth-life variables to quantify the magnitudes of direct and indirect hypothesized causal relationships
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Alzheimer’s disease (AD) is the world’s leading cause of dementia and is the sixthleading cause of death in the United States. While AD has been studied for over a century, little progress has been made in terms of treating or…
Alzheimer’s disease (AD) is the world’s leading cause of dementia and is the sixthleading cause of death in the United States. While AD has been studied for over a century, little progress has been made in terms of treating or preventing disease progression; therefore, new therapeutic drug targets must be identified. Current clinical trials focus on inhibiting Beta- Secretase 1 (BACE1), the major enzyme involved in the formation of the amyloid beta (Abeta) peptide fragments that aggregate to form insoluble plaques in the brains of AD patients. However, many of these clinical trials have been halted due to neurological effects or organ damage with no substantial cognitive improvements. Because the current leading theory of AD is that the buildup of amyloid plaques leads to metabolic changes that result in the intraneuronal accumulation of hyperphosphorylated Microtubule Associated Protein Tau (TAU, encoded by the MAPT gene), which causes cell death resulting in brain atrophy and dementia (known as the Amyloid Cascade Hypothesis), identifying drug targets that modulate Amyloid Precursor Protein (APP) processing – without directly inhibiting BACE1 – may prove to be a viable treatment. In this work, the role of the Adenosine triphosphate Binding Cassette subfamily C member 1 (ABCC1) was studied in the context of AD. Rare mutations in ABCC1 were identified in a familial case of late-onset AD and in a sporadic case of early-onset AD, and previous laboratories have demonstrated that Abeta is a substrate for ABCC1-mediated export. Although the final experiments reveal no significant difference between the mutant and reference alleles, the data demonstrate that overexpression of ABCC1 modulates APP processing, resulting in decreased Abeta formation and increased alpha- secretase cleavage of the APP molecule, likely via transcriptional modulation of genes that are capable of altering APP metabolism. Therefore, pharmacological interventions that increase either ABCC1 expression or activity may be capable of halting, reversing, or preventing disease progression. Many cancer drug development pipelines have been employed to identify compounds that decrease ABCC1 expression or activity, and it is likely that compounds have been identified that have the opposite effect. These drugs should be studied in the context of Alzheimer’s disease.
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Next-generation sequencing is a powerful tool for detecting genetic variation. How-ever, it is also error-prone, with error rates that are much larger than mutation rates. This can make mutation detection difficult; and while increasing sequencing depth can often help, sequence-specific errors and…
Next-generation sequencing is a powerful tool for detecting genetic variation. How-ever, it is also error-prone, with error rates that are much larger than mutation rates. This can make mutation detection difficult; and while increasing sequencing depth can often help, sequence-specific errors and other non-random biases cannot be de- tected by increased depth. The problem of accurate genotyping is exacerbated when there is not a reference genome or other auxiliary information available. I explore several methods for sensitively detecting mutations in non-model or- ganisms using an example Eucalyptus melliodora individual. I use the structure of the tree to find bounds on its somatic mutation rate and evaluate several algorithms for variant calling. I find that conventional methods are suitable if the genome of a close relative can be adapted to the study organism. However, with structured data, a likelihood framework that is aware of this structure is more accurate. I use the techniques developed here to evaluate a reference-free variant calling algorithm. I also use this data to evaluate a k-mer based base quality score recalibrator (KBBQ), a tool I developed to recalibrate base quality scores attached to sequencing data. Base quality scores can help detect errors in sequencing reads, but are often inaccurate. The most popular method for correcting this issue requires a known set of variant sites, which is unavailable in most cases. I simulate data and show that errors in this set of variant sites can cause calibration errors. I then show that KBBQ accurately recalibrates base quality scores while requiring no reference or other information and performs as well as other methods. Finally, I use the Eucalyptus data to investigate the impact of quality score calibra- tion on the quality of output variant calls and show that improved base quality score calibration increases the sensitivity and reduces the false positive rate of a variant calling algorithm.
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