Null Codon-Based Models of Synonymous and Nonsynonymous Substitution From a Phylogenetic Perspective.
Date of Award
Doctor of Philosophy (PhD)
Mark S. Hafner
This dissertation focuses on the relationship between codon composition and the molecular evolution of protein-coding DNA sequences. Chapter 1 emphasizes the role of codon structure in determining patterns of nucleotide substitution, as well as the influence codon composition has on the evolution of the structure and function of the protein. The overall purpose of Chapter 1 is to establish the need to study molecular evolution at the codon level. In Chapter 2, the codon-degeneracy model (CDM) of molecular evolution is constructed. This model considers codon structure in terms of patterns of nucleotide site degeneracy. It allows the prediction of patterns of substitution by considering the codon compositions of protein-coding DNA sequences, and then compares these predictions to observations inferred from phylogenetic analysis using a goodness-of-fit score as an optimality criterion. Observed data derived from the accepted phylogenetic tree of five species of pocket gopher of the genus Orthogeomys are evaluated. Chapter 3 presents a way by which the CDM can be used to choose between competing hypotheses of phylogenetic relationships. The CDM is also used to search for the optimum phylogenetic tree from among all possible topologies and configurations of phylogenetic relationship for five species of pocket gopher of the genus Orthogeomys. The CDM successfully found the accepted phylogenetic tree used in Chapter 2. Chapter 4 concentrates on the theoretical aspects of using the effects of physicochernical properties to evaluate the influences of purifying selection on patterns of nonsynonymous substitution. Paramount to this model are the residuals between expected and observed relative frequency of substitution for several Grantham difference magnitude classes. The relative effect purifying selection has on amino acid sequence evolution is quantified by calculating the sum of the positive residuals. This model is used to evaluate the differential effects of purifying selection on the three functional domains of the pocket gopher cytochrome b gene. It was found, among other things, that the transmembrane domain evolves substantially more quickly because it is largely composed of hydrophobic amino acid residues that generally possess relatively low mean potential Grantham differences.
Mcclellan, David A., "Null Codon-Based Models of Synonymous and Nonsynonymous Substitution From a Phylogenetic Perspective." (1999). LSU Historical Dissertations and Theses. 6948.