Thesis presented in fulfilment of the requirements far the degree of Master of Science in the University of the Witwatersrand. / Every organism, whether it he plant or animal, worm or man, propagates Itself with a definable degree of constancy* Such constancy cannot be entirely related to the ever-changing external environment; it becomes,of necessity, mainly an inherent function of the organism itself* Somewhere in the organism, there exists a system which determines, controls, or regulates the visible expressions of organlsmal constancy. / WHSLYP2017

No description available.

To prevent re-replication of DNA in a single cell cycle, the licensing of replication origins by Mcm2-7 is prevented during S and G2 phases. Metazoans achieve this by cell cycle regulated proteolysis of the essential licensing factor Cdt1 and formation of an inhibitory heterohexameric complex of Cdt1 with a small protein called geminin. The consequences of either stabilising Cdt1 or ablating geminin in synchronised human U2OS cells are investigated in this PhD Thesis to elucidate the possible contribution of re-replication in gene amplifications or rearrangements commonly seen in human tumours. I show that following geminin loss, cells complete an apparently normal S-phase, but a proportion arrests at the G2/M boundary. When Cdt1 starts to accumulate in these cells, DNA re-replicates, suggesting that the key role of geminin is to prevent re-licensing in G2. Inhibition of cell cycle checkpoints in cells lacking geminin promotes progression through mitosis without detectable levels of re-replication. Checkpoint kinases thereby amplify re-replication into an all-or-nothing response by delaying geminin depleted cells in G2 phase. Comparative Genomic Hybridisation (CGH) array and Solexa Deep DNA sequencing revealed that re-replication after geminin depletion does not appear at preferential genomic regions within the human genome. This is consistent with a recent observation that G2 cells have lost their replication timing information and reduplicate their genome stochastically. In contrast, when Cdt1 is stabilised by the neddylation inhibitor MLN4924, re-replication starts directly from within S-phase raising the question whether alternative mechanisms of may cause distinct genomic consequences.

No description available.

No description available.

Chromosomal evolution has long been linked with the process of organismal speciation, and many different theories have been suggested over the years to explain why this would be so. These theories can be loosely grouped into two eras. Classical chromosomal speciation models focused on negative heterosis of chromosomal rearrangements causing malsegregation and germ cell death in hybrids. More recent models examine the effects of reduced recombination around rearrangements and the impact this can have on sequence evolution, specifically the accumulation of genetic incompatibilities.¶ The huntsman spider Delena cancerides is known to be highly chromosomally variable, and to have reduced recombination near fusions. However, this species has previously only been interpreted with reference to the classical models of chromosomal speciation, the expectations of which it does not fit well. Broad-scale sampling of this spider has revealed extensive chromosomal diversity and complexity. Twenty one chromosomally differentiated populations (karyomorphs) of this spider have now been described, including those with the putatively ancestral configuration of all telocentric bivalents at meiosis (tII), and many that are saturated for Robertsonian fusions. These include up to six different karyomorphs with metacentric bivalents (mII), eight karyomorphs that form a chain of chromosomes at male meiosis, and six karyomorphs that form two separate but co-segregating chains.¶ A computer simulation was used to test hypotheses regarding the evolution of this chromosomal diversity, which indicated that fusions are likely to have accumulated gradually, possibly due to meiotic drive. Historical phylogeographic analyses have shown that deep cryptic divisions exist which are concordant with the chromosomal diversity.¶ Hybridization experiments have suggested that many hybrid zones between karyomorphs of this species are tension zones, and that genetic incompatibilities are likely to play an important role in generating partial reproductive isolation of karyomorphs. Furthermore, several hybrid zones appear to have been modified by staggered clines. The staggering of clines is thought to ameliorate reproductive isolation mechanisms that are dependent on epistatic fitness interactions, and so may prevent diverging populations progressing towards speciation. ¶Therefore, on the basis of the available evidence, D. cancerides may fit the recombination suppression model of chromosomal speciation, although it may be unlikely that the karyomorphs will progress towards full species status. Hence, this species may in the future make a highly informative model organism for investigating the early stages of genetic reproductive isolation associated with chromosomal rearrangements.

Thèse (M.Sc.)--Université Laval, 2005. / Titre de l'écran-titre (visionné le 14 mai 2007). Bibliogr.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 223-229). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 223-229). Also available on the Internet.

Thesis (Ph. D.)--University of Texas at Austin, 2003. / Vita. Includes bibliographical references. Available also from UMI Company.