3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item The molecular basis of muticellularity(2018) Featherston, JonathanThe volvocine lineage of chlorophytes is a model lineage for investigating the evolution of multicellularity, sexual dimorphism and other biological processes. Extant members of the lineage include unicellular to many celled multicellular taxa with germ-soma division of labour. Investigating the genome sequences of modern volvocines furthers our understanding of the molecular basis of multicellularity. Amongst the simplest of multicellular organisms in the lineage is the homothallic 4-celled Tetrabaena socialis, which makes it ideal for investigating the genomic basis for the initial transition to simple multicellularity. With the aim of exploring the molecular basis for the evolution of multicellularity de novo nuclear and organelle genome assemblies as well as a de novo transcriptome assembly of Tetrabaena socialis NIES-571 were generated. Comparative genomic analyses with available volvocine genomes were performed. The organelle genomes of Tetrabaena socialis were found to be highly inflated with non-coding DNA and the mitochondrial genome is circular indicating that a circular mitochondrial genome was present near the origin of multicellularity. Inflated organelle genomes are presumed be due to population genetic effects and neutral evolution. As per previous analyses of volvocine genomes comparative genomic analyses undertaken in this thesis demonstrated that the evolution of multicellularity was not associated with extensive gains in genome or proteome complexity. x Various analyses identified modifications to the ubiquitin proteasomal pathway (UPP) that were associated with the origin of multicellularity. Targeted ubiquitin-mediated degradation of cell cycle effector molecules is a potential mechanism for regulation of cell division number in the volvocine lineage. Gene families gained at the origin of multicellularity were identified and found to be enriched in developmental genes and lineage specific genes. Few genes gained are known only from multicellular organisms and, therefore, the analysis of gene family gain and loss does not support shared genetic mechanisms for multicellularity but instead that the evolution of multicellularity involved lineage specific genetic mechanisms. Mating-locus genes that in heterothallic volvocines are limited to either gender, were identified in the genome of the homothallic Tetrabaena socialis (the first homothallic taxon in the lineage to be sequenced). The presence of gender-limited mating-locus genes in the genome of Tetrabaena socialis demonstrates how a single strain can produce both plus and minus mating-types. The genome sequence of Tetrabaena socialis adds to a growing collection of volvocine genomes for analysis and as one of the simplest in the lineage it is of unique significance.Item Protein synthesis, cell division and cell death(1993) Davidoff, Avri NavaIn this study the morphologic, cytokinetic, biochemical, and molecu1w: consequences of low-dose continuous Puromycin-exposure were examined in HL-60 cells, and in a variety of malignant and non-malignant human and murine cell types. Puromycin (PM) is a composite of the amino nucleoside dimethyladenosine and tyrosine-o-methylether. Functionally it is an analogue of the terminal aminoacyl-adenosine portion of aminoacyl-tRNA, more specifically of tyrosyl..tRNA. At high concentrations 5-S0#tg/ml (10-100#tM) PM has been found to block protein synthesis completely by causing the premature release from the ribosomes of truncated peptide chains which are bound to PM through their carboxyl termini. The nascent PMGpeptide complexes (PMPs) are rapidly degraded through a ubiquitin-dependent pathway and are of interest because of (i) their potential to compete for degradation with the natural substrates of the ubiquitin-dependent pathway, including cyclin B, and (ii) because their structure predicts an inhibitory effect on tyrosine kinase activity. In the current' study then, special consideration was given to the effect of PM on the cell cycle, on apoptosis (programmed. cell death), and on tyrosine kinase activity, As a means of comparison, certain of these effects were also examined with respect to another translation inhibitor Cycloheximide (CHX), to two other substituted purines Puromycin Amino nucleoside (PAN) and 6..Dimethylaminopurine (6-DMAP), as well as to the cyclophospbamide derivative Mafosfamide (ASTA Z 7557).