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Title: Karyotype evolution in vivo and in vitro
Author: Bengtsson, Bengt Olle
ISNI:       0000 0001 3457 457X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1974
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The present thesis is divided into two parts; the first part, comprising chapters 1 to 4, called "Theoretical considerations on karyotype evolution in mammals", and the second part, chapters 5 and 6, called "Karyotype evolution in cell lines". All the chapters are selfcontained and have their own lists of references. The first three chapters deal with different population genetical aspects arising from the reduced fertility of chromosomal heterozygotes relative to chromosomal homozygotes. In chapter 1, after an introduction about karyotypes and chromosome mutations, various factors which can influence the behaviour of a chromosome mutation in a population are considered. The probabilities are given for a chromosome mutation to become fixed in a small population due to random genetic drift, and the conditions are specified under which segregation distortion, viability advantage and recombination modification can help a chromosome mutation to increase in frequency in a large, random mating population. Chapter 2 brings up to discussion the factors which determine the fertility disadvantage of chromosomal heterozygotes. The role of the reproductive system in influencing the effective fertility of individuals which produce lethal but functional gametes is stressed. In the last part of chapter 2 we describe how the fitness disadvantage associated with human chromosome mutations can be estimated. The importance of chromosome mutations in the speciation process is debated in chapter 3. According to a common idea, chromosome mutations are important for speciation because they can help to decrease the effective gene-flow between two partially separated populations. However, there are a number of problems associated with this view. The main obstacle is the rather small effect of karyotype differences on gene-flow between two populations; this is shown in chapter 3 with a simple mathematical model. The chapter ends with us turning the question around through arguing that a chromosome mutation may have a much better chance to spread in a speciation situation, which implies that speciation is important for chromosome mutations rather than the reverse. Chapter 4 is a short chapter introducing the use of nonparametric statistics to karyotype research. We here show that there exists a significantly high proportion of mammalian karyotypes containing acrocentric and bi-armed chromosomes in a non-random mixture. The result is perhaps not very surprising, but the chapter should indicate that this approach to karyotype research can be fruitfully continued, given more data and the help of a computer. The results obtained from an investigation of a series of human intraspecific hybrids made between lymphocytes and D98/AH-2 cells are described in chapter 5. The author of this thesis did most of the tissue culture work involved and the karyotype analysis. Special effort was put into determining and describing karyotypic and genetic - enzyme and immunological - markers of the hybrid cells. All the hybrid lines were karyotypically very stable, and the karyotype evolution of one line, DM, was closely followed during more than 500 days of growth in culture. A number of 6-thioguanine resistent lines were isolated, and examples are given which show how such segregant lines can be used for genetic analysis of the human genome. Established cell lines grown under constant conditions normally reach a kind of equilibrium in respect to the karyotypes of the cells in the cell line. The equilibrium is characterized by almost all cells having different but, at the same time, similar karyotypes. In chapter 6 is proposed a model which we hope can be used to describe such situations of variability and stability. Based on the idea that there is one type of cells in the cell line which is ideal and that there are many ways by which cells can differ from the ideal type of cells, this model is in certain aspects very crude. It is, however, the first model of its kind, as far as we know, and other models which try to be interpretable must probably be based on premises very similar to the ones used in chapter 6.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available