Biology Commons^™

Atypical Activation Of The G Protein Gα By The Oncogenic Mutation Q209p, Marcin Maziarz, Anthony Leyme, Arthur Marivin, Alex Luebbers, Prachi P. Patel, Zhe Chen, Stephen R. Sprang, Mikel Garcia-Marcos

Biological Sciences Faculty Publications

The causative role of G protein-coupled receptor (GPCR) pathway mutations in uveal melanoma (UM) has been well-established. Nearly all UMs bear an activating mutation in a GPCR pathway mediated by G proteins of the G family, driving tumor initiation and possibly metastatic progression. Thus, targeting this pathway holds therapeutic promise for managing UM. However, direct targeting of oncogenic Gα mutants, present in ∼90% of UMs, is complicated by the belief that these mutants structurally resemble active Gα WT. This notion is solidly founded on previous studies characterizing Gα mutants in which a conserved catalytic glutamine (Gln-209 in Gα) is replaced …

Genetics Of A De Novo Origin Of Undifferentiated Multicellularity, Matthew D. Herron, William C. Ratcliff, Jacob Boswell, Frank Rosenzweig

Biological Sciences Faculty Publications

The evolution of multicellularity was a major transition in evolution and set the stage for unprecedented increases in complexity, especially in land plants and animals. Here, we explore the genetics underlying a de novo origin of multicellularity in a microbial evolution experiment carried out on the green alga Chlamydomonas reinhardtii. We show that large-scale changes in gene expression underlie the transition to a multicellular life cycle. Among these, changes to genes involved in cell cycle and reproductive processes were overrepresented, as were changes to C. reinhardtii-specific and volvocine-specific genes. These results suggest that the genetic basis for the experimental evolution …

Streamlined Preparation Of Genomic Dna In Agarose Plugs For Pulsed-Field Gel Electrophoresis, Linda D. Hicks, Charlotte M. Van Der Graaf, Jacob Childress, Emily Cook, Karen Schmidt, Frank Rosenzweig, Eugene Kroll

Biological Sciences Faculty Publications

Genome analysis using pulsed-field gel electrophoresis (PFGE) has been used in applications ranging from typing bacterial strains to radiobiology to cancer research. While methods for running PFGE have been significantly improved since its invention, the method for preparing chromosomal DNA itself has remained essentially unchanged. This limits the applicability of PFGE, especially when analyses require many samples. We have streamlined sample preparation for routine applications of PFGE through the use of deep-well 48-well plates. Besides saving time, our protocol has the added advantage of reducing the volume of expensive reagents. Our improved protocol enables us to reduce throughput time and …

Analysis Of Motility In Multicellular Chlamydomonas Reinhardtii Evolved Under Predation, Margrethe Boyd, Frank Rosenzweig, Matthew D. Herron

Biological Sciences Faculty Publications

The advent of multicellularity was a watershed event in the history of life, yet the transition from unicellularity to multicellularity is not well understood. Multicellularity opens up opportunities for innovations in intercellular communication, cooperation, and specialization, which can provide selective advantages under certain ecological conditions. The unicellular alga Chlamydomonas reinhardtii has never had a multicellular ancestor yet it is closely related to the volvocine algae, a clade containing taxa that range from simple unicells to large, specialized multicellular colonies. Simple multicellular structures have been observed to evolve in C. reinhardtii in response to predation or to settling rate-based selection. Structures …

Deciphering The Origin, Evolution, And Physiological Function Of The Subtelomeric Arylalcohol Dehydrogenase Gene Family In The Yeast Saccharomyces Cerevisiae, Dong Dong Yang, Gustavo M. De Billerbeck, Jin Jing Zhang, Frank Rosenzweig, Jean Marie Francois

Biological Sciences Faculty Publications

Homology searches indicate that Saccharomyces cerevisiae strain BY4741 contains seven redundant genes that encode putative aryl-alcohol dehydrogenases (AAD). Yeast AAD genes are located in subtelomeric regions of different chromosomes, and their functional role(s) remain enigmatic. Here, we show that two of these genes, AAD4 and AAD14, encode functional enzymes that reduce aliphatic and aryl-aldehydes concomitant with the oxidation of cofactor NADPH, and that Aad4p and Aad14p exhibit different substrate preference patterns. Other yeast AAD genes are undergoing pseudogenization. The 5' sequence of AAD15 has been deleted from the genome. Repair of an AAD3 missense mutation at the catalytically essential Tyr73 …

Identification Of Novel Mites (Miniature Inverted-Repeat Transposable Elements) In Coxiella Burnetii: Implications For Protein And Small Rna Evolution, Shaun Wachter, Rahul Raghavan, Jenny Wachter, Michael F. Minnick

Biological Sciences Faculty Publications

Background: Coxiella burnetii is a Gram-negative gammaproteobacterium and zoonotic agent of Q fever. C. burnetii’s genome contains an abundance of pseudogenes and numerous selfish genetic elements. MITEs (miniature invertedrepeat transposable elements) are non-autonomous transposons that occur in all domains of life and are thought to be insertion sequences (ISs) that have lost their transposase function. Like most transposable elements (TEs), MITEs are thought to play an active role in evolution by altering gene function and expression through insertion and deletion activities. However, information regarding bacterial MITEs is limited.

Results: We describe two MITE families discovered during research on small non-coding …

Crystal Structure Of The Major Quadruplex Formed In The Promoter Region Of The Human C-Myc Oncogene, Sascha Stump, Tung-Chung Mou, Stephen R. Sprang, Nicholas R. Natale, Howard D. Beall

Biological Sciences Faculty Publications

The c-MYC oncogene mediates multiple tumor cell survival pathways and is dysregulated or overexpressed in the majority of human cancers. The NHE III1 region of the c-MYC promoter forms a DNA quadruplex. Stabilization of this structure with small molecules has been shown to reduce expression of c-MYC, and targeting the c-MYC quadruplex has become an emerging strategy for development of antitumor compounds. Previous solution NMR studies of the c-MYC quadruplex have assigned the major conformer and topology of this important target, however, regions outside the G-quartet core were not as well-defined. Here, we report a high-resolution crystal structure (2.35 Å) …

Avian Community Responses To Bison Grazing In North American Intermountain Grasslands, Danielle A. Fagre

Graduate Student Theses, Dissertations, & Professional Papers

Grassland and shrubland songbird species are a guild of conservation concern in North America. Many of these species have experienced severe population declines, due to habitat loss and land use change. This makes the conservation and management of remaining habitat of crucial importance for this guild. Grazing by large herbivores is an ecosystem process in grassland systems, and in North America, one of the major historic grazers was the Plains bison (Bison bison). Bison are considered ecosystem engineers, because they modify habitat to be more or less suitable for other species, such as grassland and shrubland songbirds. Bison …

Colonization Of And Adaptation To Tidal Marshes In The Savannah Sparrow (Passerculus Sandwichensis), Phred M. Benham

Graduate Student Theses, Dissertations, & Professional Papers

Intraspecific patterns of geographic variation reflect a dynamic history of colonization and divergence in response to spatially varying selective pressures. Analysis of this phenotypic variation has long stimulated biological thought, yet many outstanding questions remain regarding the ecological and evolutionary mechanisms driving patterns of geographic variation. In my dissertation, I collected data on demographic history, physiological traits contributing to salinity tolerance, and acclimation responses to different salinities to elucidate the mechanisms shaping colonization and adaptive divergence in tidal marsh populations of Savannah Sparrows (Passerculus sandwichensis). Specifically, I addressed two main questions related to adaptive divergence in this species: (1) how …

Life On The Edge: Risk Of Predation Drives Selection Of Habitat And Survival Of Neonates In Endangered Sierra Nevada Bighorn Sheep, Shannon Forshee

Graduate Student Theses, Dissertations, & Professional Papers

Long-term viability of endangered populations requires development of effective management strategies that target the population vital rate with the highest potential to influence population trajectories. When adult survival is high and stable, juvenile recruitment is the vital rate with the greatest potential to improve population trajectories. For my thesis I examined how lactating Sierra Nevada Bighorn sheep (Ovis Canadensis sierra) balance forage and predation risk during the neonatal period. I first identified resource selection strategies employed by lactating females to promote survival of neonates and then determined the primary factors affecting survival of neonates. I found lactating females selected for …

Conflicting Hydraulic Effects Of Xylem Pit Structure Relate To The Growth-Longevity Tradeoff In A Conifer Species, Beth Roskilly

Graduate Student Theses, Dissertations, & Professional Papers

Consistent with a ubiquitous life history tradeoff, trees exhibit a negative relationship between growth and longevity among and within species. However, the mechanistic basis of this life history tradeoff is not well understood. In addition to tradeoffs among multiple traits based on resource allocation conflicts, life history tradeoffs may arise from tradeoffs based on single traits under opposing selection. While a myriad of factors likely contribute to the growth-longevity tradeoff in trees, we hypothesized that conflicting functional effects of xylem structural traits contribute to the growth-longevity tradeoff. We tested this hypothesis by examining the extent to which xylem morphological traits …