Evolution of Gene Families via Gene Duplication with specific Examples in the Nucleoside Salvage Pathway.

摘要

Gene and genome duplications generate novel genetic material upon which evolution can act via a number of different mechanisms. Duplications have the potential to cause structural and functional gene and genome evolution leading to speciation, lineage-specific evolution, and adaptation. Immediately post-duplication the structure, function, duplication process, and genetic context within which the duplications occur dictate whether or not the novel copy will go to fixation via a number of different retention mechanisms, and contribute to the evolutionary history of a species, or if it will eventually be lost through population genetic forces.;In order to gain a better understanding of the dynamics of gene duplicate fixation and retention, simulation studies were performed focusing on the role neofunctionalization, subfunctionalization, and dosage balance constraints play during the fixation phase and long-term retention of gene duplicates. Following the fixation of complete gene-interaction networks, neo- and subfunctionalization, as well as dosage balance constraints generated identifiable trends of loss over time. This finding supports the notion of incorporating trends of gene loss over time into mechanistic models for gene family analysis. A simulation of the small scale duplication process and subsequent trends of duplicate retention and fixation within the population under different population genetic pressures and gene structure provided a comprehensive view of how segregating genotypic diversity of populations due to differing mutational processes (duplication, nonfunctionalizing, and beneficial mutation) is affected under different models of retention. Furthermore, the predominant fixation and retention mechanism differs depending of duplicate length, mutational rates, and gene structure, and ploidy.;Functional divergence between duplicate copies is one process underlying gene family Iexpansion. In order to study trends of gene duplicate divergence, gene family analyses were conducted on enzyme families of the nucleoside salvage pathway. The broad phylogenetic distribution and lineage-specific differences in gene family members present in different genomes makes these gene families particularly interesting to study in light of gene duplications and losses. In general, the different enzyme classes within the different gene families evolved through a number of key duplications followed by substrate specificity divergence. Structural studies suggest that while changes in the active site residues between gene duplicates may contribute to substrate specialization, residues outside the active site with effects on topology may have played an equally important role. Lineage-specific losses post-duplications further affected the evolution of enzyme classes, as complements of gene family members differ between major clades of organisms. These losses may have led to further remodeling of enzymes in order to reattain functionality lost through lineage specific paralog loss post-divergence.