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Description
Skeletal muscles arise from the myotome compartment of the somites that form during vertebrate embryonic development. Somites are transient structures serve as the anlagen for the axial skeleton, skeletal muscle, tendons, and dermis, as well as imposing the metameric patterning of the axial musculoskeletal system, peripheral nerves, and vasculature. Classic studies have described the role of Notch, Wnt, and FGF signaling pathways in controlling somite formation and muscle formation. However, little is known about the transformation of myotome compartments into identifiable post-natal muscle groups. Using a mouse model, I have undertaken an evaluation of morphological events, including hypertrophy and hyperplasia, related to the formation of several muscles positioned along the dorsal surface of the vertebrae and ribs. Lunatic fringe (Lfng) deficient embryos and neonates were also examined to further understand the role of the Notch pathway in these processes as it is a modulator of the Notch receptor and plays an important role in defining somite borders and anterior-posterior patterning in many vertebrates. Lunatic fringe deficient embryos showed defects in muscle fiber hyperplasia and hypertrophy in the iliocostalis and longissimus muscles of the erector spinae group. This novel data suggests an additional role for Lfng and the Notch signaling pathway in embryonic and fetal muscle development.
ContributorsDe Ruiter, Corinne (Author) / Rawls, J. Alan (Thesis advisor) / Wilson-Rawls, Jeanne (Committee member) / Kusumi, Kenro (Committee member) / Fisher, Rebecca E. (Committee member) / Arizona State University (Publisher)
Created2012
Description
Understanding the diversity, evolutionary relationships, and geographic distribution of species is foundational knowledge in biology. However, this knowledge is lacking for many diverse lineages of the tree of life. This is the case for the desert stink beetles in the tribe Amphidorini LeConte, 1862 (Coleoptera: Tenebrionidae) – a lineage of arid-adapted flightless beetles found throughout western North America. Four interconnected studies that jointly increase our knowledge of this group are presented. First, the darkling beetle fauna of the Algodones sand dunes in southern California is examined as a case study to explore the scientific practice of checklist creation. An updated list of the species known from this region is presented, with a critical focus on material now made available through digitization and global aggregation. This part concludes with recommendations for future biodiversity checklist authors. Second, the psammophilic genus Trogloderus LeConte, 1879 is revised. Six new species are described, and the first, multi-gene phylogeny for the genus is inferred. In addition, historical biogeographic reconstructions along with novel hypotheses of speciation patterns within the Intermountain Region are given. In particular, the Kaibab Plateau and Kaiparowitz Formation are found to have promoted speciation on the Colorado Plateau. The Owens Valley and prehistoric Bouse Embayment are similarly hypothesized to drive species diversification in southern California. Third, a novel phylogenomic analysis for the tribe Amphidorini is presented, based on 29 de novo partial transcriptomes. Three putative ortholog sets were discovered and analyzed to infer the relationships between species groups and genera. The existing classification of the tribe is found to be highly inadequate, though the earliest-diverging relationships within the tribe are still in question. Finally, the new phylogenetic framework is used to provide a genus-level revision for the Amphidorini, which previously contained six valid genera and 253 valid species. This updated classification includes more than 100 taxonomic changes and results in the revised tribe consisting of 16 genera, with three being described as new to science.
ContributorsJohnston, Murray Andrew (Author) / Franz, Nico M (Thesis advisor) / Cartwright, Reed (Committee member) / Taylor, Jesse (Committee member) / Pigg, Kathleen (Committee member) / Arizona State University (Publisher)
Created2018
Description
Isolation-by-distance is a specific type of spatial genetic structure that arises when parent-offspring dispersal is limited. Many natural populations exhibit localized dispersal, and as a result, individuals that are geographically near each other will tend to have greater genetic similarity than individuals that are further apart. It is important to identify isolation-by-distance because it can impact the statistical analysis of population samples and it can help us better understand evolutionary dynamics. For this dissertation I investigated several aspects of isolation-by-distance. First, I looked at how the shape of the dispersal distribution affects the observed pattern of isolation-by-distance. If, as theory predicts, the shape of the distribution has little effect, then it would be more practical to model isolation-by-distance using a simple dispersal distribution rather than replicating the complexities of more realistic distributions. Therefore, I developed an efficient algorithm to simulate dispersal based on a simple triangular distribution, and using a simulation, I confirmed that the pattern of isolation-by-distance was similar to other more realistic distributions. Second, I developed a Bayesian method to quantify isolation-by-distance using genetic data by estimating Wright’s neighborhood size parameter. I analyzed the performance of this method using simulated data and a microsatellite data set from two populations of Maritime pine, and I found that the neighborhood size estimates had good coverage and low error. Finally, one of the major consequences of isolation-by-distance is an increase in inbreeding. Plants are often particularly susceptible to inbreeding, and as a result, they have evolved many inbreeding avoidance mechanisms. Using a simulation, I determined which mechanisms are more successful at preventing inbreeding associated with isolation-by-distance.
ContributorsFurstenau, Tara N (Author) / Cartwright, Reed A (Thesis advisor) / Rosenberg, Michael S. (Committee member) / Taylor, Jesse (Committee member) / Wilson-Sayres, Melissa (Committee member) / Arizona State University (Publisher)
Created2015
Description
The most abundantly studied societies, with the exception of humans, are those of the eusocial insects, which include all ants. Eusocial insect societies are typically composed of many dozens to millions of individuals, referred to as nestmates, which require some form of communication to maintain colony cohesion and coordinate the activities within them. Nestmate recognition is the process of distinguishing between nestmates and non-nestmates, and embodies the first line of defense for social insect colonies. In ants, nestmate recognition is widely thought to occur through olfactory cues found on the exterior surfaces of individuals. These cues, called cuticular hydrocarbons (CHCs), comprise the overwhelming majority of ant nestmate profiles and help maintain colony identity. In this dissertation, I investigate how nestmate recognition is influenced by evolutionary, ontogenetic, and environmental factors. First, I contributed to the sequencing and description of three ant genomes including the red harvester ant, Pogonomyrmex barbatus, presented in detail here. Next, I studied how variation in nestmate cues may be shaped through evolution by comparatively studying a family of genes involved in fatty acid and hydrocarbon biosynthesis, i.e., the acyl-CoA desaturases, across seven ant species in comparison with other social and solitary insects. Then, I tested how genetic, developmental, and social factors influence CHC profile variation in P. barbatus, through a three-part study. (1) I conducted a descriptive, correlative study of desaturase gene expression and CHC variation in P. barbatus workers and queens; (2) I explored how larger-scale genetic variation in the P. barbatus species complex influences CHC variation across two genetically isolated lineages (J1/J2 genetic caste determining lineages); and (3) I experimentally examined how CHC development is influenced by an individual’s social environment. In the final part of my work, I resolved discrepancies between previous findings of nestmate recognition behavior in P. barbatus by studying how factors of territorial experience, i.e., spatiotemporal relationships, affect aggressive behaviors among red harvester ant colonies. Through this research, I was able to identify promising methodological approaches and candidate genes, which both broadens our understanding of P. barbatus nestmate recognition systems and supports future functional genetic studies of CHCs in ants.
ContributorsCash, Elizabeth I (Author) / Gadau, Jürgen (Thesis advisor) / Liebig, Jürgen (Thesis advisor) / Fewell, Jennifer (Committee member) / Hölldobler, Berthold (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2016
Description
The complex life cycle and widespread range of infection of Plasmodium parasites, the causal agent of malaria in humans, makes them the perfect organism for the study of various evolutionary mechanisms. In particular, multigene families are considered one of the main sources for genome adaptability and innovation. Within Plasmodium, numerous species- and clade-specific multigene families have major functions in the development and maintenance of infection. Nonetheless, while the evolutionary mechanisms predominant on many species- and clade-specific multigene families have been previously studied, there are far less studies dedicated to analyzing genus common multigene families (GCMFs). I studied the patterns of natural selection and recombination in 90 GCMFs with diverse numbers of gene gain/loss events. I found that the majority of GCMFs are formed by duplications events that predate speciation of mammal Plasmodium species, with many paralogs being neutrally maintained thereafter. In general, multigene families involved in immune evasion and host cell invasion commonly showed signs of positive selection and species-specific gain/loss events; particularly, on Plasmodium species is the simian and rodent clades. A particular multigene family: the merozoite surface protein-7 (msp7) family, is found in all Plasmodium species and has functions related to the erythrocyte invasion. Within Plasmodium vivax, differences in the number of paralogs in this multigene family has been previously explained, at least in part, as potential adaptations to the human host. To investigate this I studied msp7 orthologs in closely related non-human primate parasites where homology was evident. I also estimated paralogs’ evolutionary history and genetic polymorphism. The emerging patterns where compared with those of Plasmodium falciparum. I found that the evolution of the msp7 multigene family is consistent with a Birth-and-Death model where duplications, pseudogenization and gene lost events are common. In order to study additional aspects in the evolution of Plasmodium, I evaluated the trends of long term and short term evolution and the putative effects of vertebrate- host’s immune pressure of gametocytes across various Plasmodium species. Gametocytes, represent the only sexual stage within the Plasmodium life cycle, and are also the transition stages from the vertebrate to the mosquito vector. I found that, while male and female gametocytes showed different levels of immunogenicity, signs of positive selection were not entirely related to the location and presence of immune epitope regions. Overall, these studies further highlight the complex evolutionary patterns observed in Plasmodium.
ContributorsCastillo Siri, Andreina I (Author) / Rosenberg, Michael (Thesis advisor) / Escalante, Ananias (Committee member) / Taylor, Jesse (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2016
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
Biogeography places the geographical distribution of biodiversity in an evolutionary context. Ants (Hymenoptera: Formicidae), being a group of ubiquitous, ecologically dominant, and diverse insects, are useful model systems to understand the evolutionary origins and mechanisms of biogeographical patterns across spatial scales. On a global scale, ants have been used to test hypotheses on the origin and maintenance of the remarkably consistent latitudinal diversity gradient where biodiversity peaks in the equatorial tropics and decreases towards the poles. Additionally, ants have been used to posit and test theories of island biogeography such as the mechanisms of the species-area relationship, being the increase of biodiversity with cumulative land area. However, there are still unanswered questions about ant biogeography such as how specialized life histories contribute to their global biogeographical patterns. Furthermore, there remain island systems in the world’s biodiversity hotspots that harbor much less ant species than predicted by the species-area relationship, which potentially suggests a place ripe for discovery. In this dissertation, I use natural history, taxonomic, geographic, and phylogenetic data to study ant biodiversity and biogeography across spatial scales. First, I study the global biodiversity and biogeography of a specialized set of symbiotic interactions between ant species, here referred to as myrmecosymbioses, with an emphasis on social parasitism where one species exploits the parental care behavior and social colony environment of another species. In addition to characterizing a new myrmecosymbiosis, I use a global biogeographic and phylogenetic dataset to show that ant social parasitism is distributed along an inverse latitudinal diversity gradient where species richness and independent evolutionary origins of social parasitism peak within the northern hemisphere where the least free-living ant diversity exists. Second, I study the unexplored ant fauna of the Vanuatuan archipelago in the South Pacific. Using approximately 10,000 Vanuatuan ant specimens coupled with phylogenomics, I fill in a historical knowledge gap of South Pacific ant biogeography and demonstrate that the Vanuatuan ant fauna is a novel biodiversity hotspot. With these studies, I provide insights into how specialized life histories and unique island biotas shape the global distribution of biodiversity in different ways, especially in the ants.
ContributorsGray, Kyle William (Author) / Rabeling, Christian (Thesis advisor) / Martins, Emilia (Committee member) / Taylor, Jesse (Committee member) / Pratt, Stephen (Committee member) / Wojciechowski, Martin (Committee member) / Arizona State University (Publisher)
Created2023
Description
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.
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.
ContributorsOrr, Adam James (Author) / Cartwright, Reed (Thesis advisor) / Wilson, Melissa (Committee member) / Kusumi, Kenro (Committee member) / Taylor, Jesse (Committee member) / Pfeifer, Susanne (Committee member) / Arizona State University (Publisher)
Created2020
Description
Satellite cells are adult muscle stem cells that activate, proliferate, and differentiate into myofibers upon muscle damage. Satellite cells can be cultured and manipulated in vitro, and thus represent an accessible model for studying skeletal muscle biology, and a potential source of autologous stem cells for regenerative medicine. This work summarizes efforts to further understanding of satellite cell biology, using novel model organisms, bioengineering, and molecular and cellular approaches. Lizards are evolutionarily the closest vertebrates to humans that regenerate entire appendages. An analysis of lizard myoprogenitor cell transcriptome determined they were most transcriptionally similar to mammalian satellite cells. Further examination showed that among genes with the highest level of expression in lizard satellite cells were an increased number of regulators of chondrogenesis. In micromass culture, lizard satellite cells formed nodules that expressed chondrogenic regulatory genes, thus demonstrating increased musculoskeletal plasticity. However, to exploit satellite cells for therapeutics, development of an ex vivo culture is necessary. This work investigates whether substrates composed of extracellular matrix (ECM) proteins, as either coatings or hydrogels, can support expansion of this population whilst maintaining their myogenic potency. Stiffer substrates are necessary for in vitro proliferation and differentiation of satellite cells, while the ECM composition was not significantly important. Additionally, satellite cells on hydrogels entered a quiescent state that could be reversed when the cells were subsequently cultured on Matrigel. Proliferation and gene expression data further indicated that C2C12 cells are not a good proxy for satellite cells. To further understand how different signaling pathways control satellite cell behavior, an investigation of the Notch inhibitor protein Numb was carried out. Numb deficient satellite cells fail to activate, proliferate and participate in muscle repair. Examination of Numb isoform expression in satellite cells and embryonic tissues revealed that while developing limb bud, neural tube, and heart express the long and short isoforms of NUMB, satellite cells predominantly express the short isoforms. A preliminary immunoprecipitation- proteomics experiment suggested that the roles of NUMB in satellite cells are related to cell cycle modulation, cytoskeleton dynamics, and regulation of transcription factors necessary for satellite cell function.
ContributorsPalade, Joanna (Author) / Wilson-Rawls, Norma (Thesis advisor) / Rawls, Jeffrey (Committee member) / Kusumi, Kenro (Committee member) / Newbern, Jason (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2020
Description
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.
ContributorsMaag, Garett (Author) / Dolby, Greer A. (Thesis advisor) / Kusumi, Kenro (Thesis advisor) / Stokes, Maya F. (Committee member) / Barly, Anthony (Committee member) / Arizona State University (Publisher)
Created2023