<p> Bamboo corals are a family (Isididae Lamouroux, 1812) of cnidarian anthozoans in the subclass Octocorallia. They are distinct and easily recognizable because of their unique articulating skeleton, which alternates internodes of calcium carbonate with proteinaceous sclerite (microscopic skeletal elements)-free nodes, and which is currently the primary synapomorphy for the family. Isididae is further divided into four subfamilies (Circinisidinae, Isidinae, Keratoisidinae, Mopseinae) based on several characters, including sclerite shape, size, and placement, and skeleton morphology. The deep-sea bamboo corals are classified in the most morphologically diverse subfamily, Keratoisidinae Gray, 1970. Currently, there are eight genera within the subfamily, and they are primarily distinguished based on branching pattern. Members of the subfamily are found worldwide and at depths greater than 200 m. I use genetic data to evaluate the monophyly of the Isididae, the relationships of the subfamilies to each other and other octocorals, and the monophyly of the genera within the Keratoisidinae. One genus, <i>Acanella,</i> is a genetically monophyletic group with a distinct polyp morphology with needle-like sclerites running obliquely up the polyp body. Additionally, I propose an evaluation of the taxonomic ranks of the bamboo corals at the family, subfamily, genus, and species levels based on morphological characters, mitochondrial genome arrangement, and <i> mtMutS</i> haplotypes. Re-description and classification is needed at every taxonomic level to fully describe and capture the morphological and genetic diversity observed.</p>

<p> Modern biological research is currently canalized into two main modes of research: detailed, mechanistic descriptions, or big data collection and statistical descriptions. The former has the advantage of being conceptually tractable and fitting into an existing scientific paradigm. However, these detailed descriptions can suffer from an inability to be understood in the larger context of biological phenomena. On the other hand, the big data approaches, while closer to being able to capture the full depth of biological complexity, are limited in their ability to impart conceptual understanding to researchers. We put forward examples of an intermediate approach. The goal of this approach is to develop models which can be understood as abstractions of biological phenomena, while simultaneously being conducive to modeling and computational approaches. Firstly, we attempt to examine the phenomenon of modularity. Modularity is an ubiquitous phenomenon in biological systems, but its etiology is poorly understood. It has been previously shown that organisms that evolved in environments with lower levels of stability tend to display more modular organization of their gene regulatory networks, although theoretical predictions have failed to account for this. We put forward a neutral evolutionary model, where we posit the process of genome expansion through gene duplications acts as a driver for the evolution of modularity. This process occurs through the duplication of regulatory elements alongside the duplication of a gene, causing sub-networks to be generated which are more tightly coupled internally than externally, which gives rise to a modular architecture. Finally, we also generate an experimental system by which we can verify our model of the evolution of modularity. Using a long term experimental evolution setup, we evolve <i>E. coli</i> under fluctuating temperature environments for 600 generations in order to test if there is a measurable increase in the modularity of the gene regulatory networks of the organisms. This data will also be used in the future to test other hypotheses related to evolution under fluctuating environments. The second such model is a computational model of the properties of bacterial growth as a function of temperature. We describe a model composed of a chain of enzyme like actions, where the output of each enzyme in the chain becomes the substrate of the following enzyme. Using well known temperature dependence curves for enzyme activity and no further assumptions, we are then able to replicate the salient properties of bacterial growth curves at varying temperatures, including lag time, carrying capacity, and growth rate. Lastly, we extend these models to attempt to describe the ability of cancer cells to alter their phenotypes in ways that would be impossible for normal cells. We term this model the <i>phenotypically pliant cells</i> model and show that it can encapsulate important aspects of cancer cell behavior.</p><p>

<p> Taxonomic checklists are a fundamental and widely-used product of taxonomy, providing a list of recognized taxa within a taxonomic group in a particular geographical area. Series of taxonomic checklists provide snapshots of recognized taxa over a period of time. Identifying and classifying the changes between these checklists can provide information on rates of name, synonym and circumscription change and can improve aggregation of datasets reconciled to different checklists.</p><p> To demonstrate this, I used a series of North American bird checklists to test hypotheses about drivers of splitting rates in North America birds. In particular, I asked if splitting was predominantly undoing previous lumping that happened during the heyday of the modern synthesis. I found that bird species have been split at an accelerating rate since the 1980s. While this was partially the result of previously lumped species being resplit, most splits were unrelated to previous lumps and thus represent new discoveries rather than simply the undoing of previous circumscription changes. I also used a series of North American freshwater algal checklists to measure stability over fifteen years, and found that 26% of species names were not shared or synonymized over this period. Rates of synonymization, lumping or splitting of species remained flat, a marked difference from North American birds. Species that were split or lumped (7% of species considered) had significantly higher abundance than other species in the USGS NAWQA dataset, a biodiversity database that uses these checklists as an index. They were associated with 19% of associated observations, showing that a small number of recircumscribed species could significantly affect interpretation of biodiversity data.</p><p> To facilitate this research, I developed a software tool that could identify and annotate taxonomic changes among a series of checklists, and could use this information to aggregate biodiversity data, which will hopefully facilitate similar research in the future. My dissertation demonstrates the value of taxonomic checklists series to answer specific questions about the drivers of taxonomic change ranging from philosophical and technical changes to characteristics of species themselves such as their abundance.</p><p>

The modern study of the origins and evolution of the group Cetacea (whales and porpoises) began with a key work published in 1966 which named an archaic group of ungulates, the Mesonychids, as the ancestors of Cetacea. Since that time, the use of both morphological and molecular techniques have split systematists into two camps. Morphological and molecular data have led workers to believe that the closest extant relatives of Cetacea are Artiodactyla, the even-toed ungulates, although a few morphologists believe that it is the Perissodactyla, the odd-toed ungulates. Later molecular studies indicate that Cetaceans are not only closely related to Artiodactyla, but may be members of that group and further, that their closest relative may be the Hippopotamus. Although the Hippopotamus hypothesis is controversial, the evidence supporting it is compelling. The idea merits serious consideration, and it may be that the morphological evidence needs to be re-evaluated.

<p> SEM observations have revealed unknown and previously undetected stages of the bloom-forming dinoflagellate Prorocentrum growing inside calcium carbonate-encrusted perithallial cells of the rhodolith-forming Lithothamnion sp. (Hapalidiaceae, Hapalidiales, Rhodophyta) in the NW Gulf of Mexico. Roundish structures inside the coralline cells were clustered together, surrounded by a thin membrane. Organized blebs, projections of the cytoplasm into the plasma membrane, as well as a suite of varying extracellular ornamentation patterns, were observed. Openings on the surface of some of the structures looked like characteristic thecal pores found in thecal plates of some dinoflagellates. DNA was extracted from inside the rhodolith and sequenced using dinoflagellate-specific cob1-primers. When blasting the resulting DNA sequences, it proved to be an exact match for Prorocentrum lima. Cells were isolated from inside the rhodoliths and cultured, revealing the presence of another set of endolithic life stages identified as Haptophyta (Prymnesiophyta), confirmed by single cell 18S rDNA sequencing. This research illustrates and illuminates newly found benthic life history stages of two ecologically important taxa of primary producers that also cause harmful algal blooms, such as the formation of red tides, fish kills, or shellfish poisoning events in the Gulf of Mexico. </p>

<p> Several new discoveries in <i>Euphorbia</i> L. subg. <i> Chamaesyce</i> Raf. sect. <i>Anisophyllum</i> Roeper for the Trans-Pecos region of Texas are documented. These include <i>E. ophthalmica </i> Pers., a species new to the Trans-Pecos from Marfa, Presidio County; <i> E. abramsiana</i> L.C. Wheeler new to Texas from Brewster and Presidio Counties; <i>E. vermiculata</i> Raf., new to Texas from Alpine, Brewster County; <i>E. cryptorubra</i> N.C. Taylor &amp; M. Terry, a newly described species from southern Hudspeth County and northern Chihuahua, Mexico; notes on <i>E. golondrina</i> L.C. Wheeler including two potential novelties; and notes on <i>E. fendleri</i> Torr. &amp; A. Gray, a problematic species complex. The sections concerning <i>E. abramsiana</i> and <i>E. cryptorubra</i> have been published Taylor and Terry (2016) in Phytoneuron and the Journal of the Botanical Institute of Texas respectively. Within <i>E. golondrina</i> and <i> E. fendleri,</i> there is much room for study, and directions for future investigations are indicated. Provided at the end is a key to all species now known for the Trans-Pecos region of Texas.</p>

<p> The brachyuran superfamily Palicoidea &Scaron;tev&ccaron;i&cacute;, 2005, commonly referred to as stilt-crabs, currently includes the families Crossotonotidae Moosa and Ser&eacute;ne, 1981 and Palicidae Bouvier, 1898, consisting of two and nine genera, respectively. Both genus and species level relationships remain largely enigmatic and are based primarily upon highly variable morphological characters. Molecular phylogenetic analyses, based on COI and 16S mitochondrial gene sequences, are used to clarify relationships among primarily western Atlantic species and to independently validate diagnostic morphological characters. The resultant molecular phylogenetic tree resolves three major clades: one grouping <i>Palicus affinis, Palicus alternatus,</i> and <i> Palicus bahamensis;</i> a second grouping <i>Palicus faxoni</i> and <i>Palicus obesus;</i> and the third grouping <i>Crossotonotus </i> sp., <i>Pseudopalicus</i> sp., <i>Palicus cristatipes, </i> and <i>Palicus sica.</i> Putative specimens of <i> P. floridanus</i> were positioned as sister species to other groups. Molecular phylogenetic evidence infers intrageneric evolutionary history of <i> Palicus</i> Philippi, 1838, concordant with relationships suggested by gonopod morphology of congeners. Gonopod morphology was found to be highly conserved within species, moderately conserved among species sharing a common clade, and divergent among species in different well-separated clades. Conversely, many morphological characters that have historically been applied to describe and identify palicids were found to be highly variable within species, inconsistently variable among species, and in some cases relatively conserved across divergent clades. On the basis of present molecular phylogenetic analyses, separation of the families Crossotonotidae and Palicidae may be supported only if further revisions to membership of the family Palicidae were to be undertaken. These revisions are deferred pending more robust genetic analyses.</p>

<p> The integration of advances in computing technology with major innovations in sequence data collection and phylogenetic inference has revolutionized evolutionary biology in the 21^st century. In particular, the continual development of both theory and software that allow for more flexibility in utilizing molecular clock methods has radically transformed our understanding of the mode and tempo of diversification across the Tree of Life. Over the course of five chapters, this dissertation explores methodological challenges to phylogenetic inference with the aim of better understanding the evolutionary history of the Holocentridae (squirrelfishes and soldierfishes). </p><p> Chapter 1 begins by focusing on the problem of accommodating clade specific rate heterogeneity in molecular clock analyses. While various nucleotide substitution models have been developed to accommodate among lineage rate heterogeneity, recently developed "uncorrelated relaxed clock" and "random local clock" models are predicted to perform better in the presence of lineage specific rate heterogeneity as these models relax assumptions of inheritance of nucleotide substitution rates between descendant lineages. Using simulations and two cetacean (whale and dolphin) datasets as a case study, we demonstrate abrupt changes in rate isolated to one or a few lineages in the phylogeny can mislead rate and age estimation, even when the node of interest is calibrated; and provide suggestions for diagnosing extreme clade specific rate heterogeneity.</p><p> Homoplasy is another important, yet often overlooked, source of error in phylogenetic studies. Chapters 2 and 3 utilize phylogenetic informative approaches to screen nucleotide sequence data for homoplasious site patterns. Using phylogenetic informativeness profiles, chapter 2 reconciles two competing hypotheses of ray-finned fish divergence times by highlighting that mitogenomic based Jurassic and Triassic divergence time estimates for most major lineages of spiny-rayed (acanthomorph) fishes were an artifact of tree extension. Evolutionary relationships of early diverging acanthomorph fishes are also contentious, with molecular data supporting either holocentrids or a clade comprised of holocentrids and primarily deep-sea fishes as the sister lineage to the species-rich percomorpha. Chapter 3 reveals this conflict to also be largely driven by homoplasy and reconciles results based on previously published data with a 132 gene next-generation sequence dataset to identify the sister lineage of percomorph and the phylogenetic placement of holocentrid fishes.</p><p> Chapter 4 continues to explore holocentrid evolutionary relationships. Using a multi-locus dataset that includes all but one holocentrid genus, this chapter provides the first molecular phylogeny of the group. The systematics of holocentrid fishes has unstable for over 100 years. We demonstrate several of the key synapomorphies for holocentrid genera are in fact homoplasious. Likewise, several genera of holocentrine (squirrelfish) are rendered consistently paraphyletic by a series of maximum-likelihood and Bayesian analyses and we propose taxonomic revisions to reflect shared ancestry.</p><p> Chapter 5 further investigates the temporal history of holocentrid evolution. Contemporary holocentrid species richness is concentrated in the Indo-Australian Archipelago (IAA), yet these fishes also represent some of the most numerous fossil taxa in deposits of the Eocene West Tethyan biodiversity hotspot. Using likelihood-based methods integrated with a molecular timetree that incorporates fossils as tip taxa, we reconstruct the history of range evolution for these fishes. Following the collapse of the West Tethys, holocentrids exhibit a signature of increased range fragmentation, becoming isolated between the Atlantic and Indo-Pacific Ocean basins. However, rather than originating within the emerging IAA hotspot, the IAA appears to have acted as a reservoir for holocentrid diversity that originated in adjacent regions over deep evolutionary timescales. By integrating extinct lineages, these results provide a necessary historic perspective on the formation and maintenance of global marine biodiversity. </p>

Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Chao Tang. Includes supplementary digital materials.

<p> The <i>BRCA1</i> and <i>BRCA2</i> (<i>BRCA</i>) genes are two tumor suppressors that when mutated, predispose patients to breast and ovarian cancer. The <i>BRCA</i> genes encode proteins that mediate the repair of DNA double strand breaks. Functional loss of the <i> BRCA</i> genes is detrimental to the integrity of the genome because without access to functional <i>BRCA</i> protein, inefficient and error-prone repair pathways are used instead. These pathways, such as Non-homologous end joining, do not accurately repair the DNA, which can introduce mutations and genomic rearrangements. Ultimately the genome is not repaired faithfully and the predisposition to cancer greatly increases. In addition to their contribution to DNA repair, the <i>BRCA</i> genes have been shown to have transcriptional activity, and this functional role can also be a driving factor behind the tumor suppressor activity.</p><p> Robustness is the ability of a complex system to sustain viability despite perturbations to it. In the context of a complex disease such as cancer, robustness gives cancers the ability to sustain uncontrollable growth and invasiveness despite treatments such as chemotherapy that attempt to eliminate the tumor. A complex system is robust however can be fragile to perturbations that the system not optimized against. In cancers, these fragilities have the potential to be cancer specific targets that can eradicate the disease specifically. </p><p> Patients with mutations in <i>BRCA</i> tend to have breast and ovarian cancers that are difficult to treat; chemotherapy is the only option and no targeted therapies are available. Targeting the synthetic lethal interaction (SLI), a mechanism of robustness, between <i>BRCA</i> and <i>PARP1</i> genes was clinically effective in treating BRCA-mutated breast and ovarian cancers. This suggests that understanding robustness in cancers can reveal potential cancer specific therapies.</p><p> In this thesis, a computational approach was developed to identify candidate mechanisms of robustness in <i>BRCA</i>-mutated breast and ovarian cancers using the publicly accessible patient gene expression and mutation data from the Cancer Genome Atlas (TCGA). Results showed that in ovarian cancer patients with a <i>BRCA2</i> mutation, the expression of genes that function in the DNA damage response were kept at stable expression state compared to those patients without a mutation. The stable expression of genes in the DNA damage response may highlight a SLI gene network that is precisely controlled. This result is significant as disrupting this precision can potentially lead to cancer specific death. In breast cancers, genes that were differentially expressed in patients with <i>BRCA</i> mutations were identified. A Bayesian network was performed to infer candidate interactions between <i> BRCA1</i> and <i>BRCA2</i> and the differentially expressed <i> FLT3, HOXA11, HPGD, MLF1, NGFR, PLAT,</i> and <i>ZBTB16</i> genes. These genes function in processes important to cancer progression such as apoptosis and cell migration. The connection between these genes with BRCA may highlight how the BRCA genes influence cancer progression.</p><p> Taken together, the findings of this thesis enhance our understanding of the <i>BRCA</i> genes and their role in DNA damage response and transcriptional regulation in human breast and ovarian cancers. These results have been attained from systems-level models to identify candidate mechanisms underlying robustness of cancers. The work presented predicts interesting candidate genes that may have potential as drug targets or biomarkers in <i> BRCA</i>-mutated breast and ovarian cancers.</p><p>