Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Accurate and comprehensive measurement of the extent and pattern of nucleotide diversity is necessary to refine theories on the dynamics of evolution. It is possible to determine the sequence of any genomic region for numerous individuals using the polymerase chain reaction (PCR) and associated techniques of DNA sequence analysis. The two regions of the human genome examined in this study were the third exon of the highly conserved (two major alleles) alcohol dehydrogenase, Adh2 locus and the second exon of the highly polymorphic (26 alleles) human leukocyte antigen, HLA-DQ{dollar}\beta{dollar}1 gene. Sequence information was determined from 25 individuals from Southwestern Ontario and 26 Dogrib individuals from the Northwest Territories of Canada. The Southwestern Ontario population is heterogeneous in ancestry and predominantly European while the Dogrib population is homogeneous and of Asian ancestry. Intra-allelic nucleotide diversity was characterized at two regions of the genome in two different human populations using PCR with direct sequencing and chaos representation of sequence organization.;No intra-allelic variation was observed in the 39,000 nucleotides examined for both exons. There was no evidence for higher substitution rates for highly polymorphic loci. The maintenance of a large number of alleles at the HLA-DQ{dollar}\beta{dollar}1 locus in populations is attributed to selective forces, in particular heterozygote advantage, while admixture and stochastic forces such as founder effects, and bottlenecks could account for observed population-specific allele frequencies at the two loci. Nucleotide diversity was nonrandom and influenced by nearest-neighbor nucleotide associations. Dinucleotide representation also accounted for the major features of the global organization in DNA sequences. Analysis of 56 large sequences from 10 species, 28 mitochondrial DNAs and 31 viral genomes identified, for the first time, that the global structure of DNA is under selective constraints that are genome-type specific and related to an as yet unknown force(s) or factor(s).;Selection plays a predominant role in determining the gene-specific variability and genome-type specific sequentiality of DNA. Thus, the evolution of the DNA sequence of a gene or genome should be viewed in the dual context of the constraints on its specific function and the genome-type specific global organization.



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