EVOLUTION OF GENOME ORGANIZATION IN ANIMALS AND YEASTS
Nakhleh, Luay K.
Doctor of Philosophy
This dissertation focus on one fundamental question: Does it matter where a gene reside on a chromosome? To answer this question, we further asked two questions that are more lineage-specific: Could the large-scale patterns of genome organization across animal species give us new insights to the underling mechanisms of genome evolution? Is there any kind of universal evolutionary patterns of genome organization among yeasts? To answer the first question, we developed a simple model of genome evolution that can explain conservation of macrosynteny (chromosome-scale gene linkage relationships) across diverse metazoan species. Many metazoan genomes preserve macrosynteny from the common ancestor of multi-cellular animal life, but the evolutionary mechanism responsible for this conservation is still unknown. We show that a simple model of genome evolution, in which Double Cut and Join (DCJ) moves are allowed only if they maintain chromosomal linkage among a set of constrained genes, can simultaneously account for the level of macrosynteny conservation observed from pair wise genome comparison and for correlated conservation among multiple species. Results from biological correlation tests prove dosage-sensitive genes are good candidates for these constrained genes and thus suggest that constraints on gene dosage may have acted over long evolutionary timescales to constrain chromosomal reorganization in metazoan genomes. For the second question, we found that fission yeasts show highly conserved genome architecture, compared to budding yeasts. Despite similar rates of sequence divergence, both gene contents and genome organizations are much more conserved in fission yeasts than in budding yeasts. The rate of gene order divergence in fission yeasts is about four times slower than that of budding yeasts. Also, comparing to budding yeasts, gene duplication events among fission yeasts are more synchronized, mainly limited to fewer function categories and significantly enriched in the subtelomeric regions of chromosomes. These results suggested that highly conserved genome organization and lack of gene content innovation might play important roles in constraining the species diversification within fission yeasts. This dissertation established an innovative computational framework for efficiently developing models of genome evolution based on observed patterns from real genome comparisons. Also, it revealed comprehensive evolutionary patterns of genome organization across yeast species and provided insights into the relative importance of point mutations and large-scale genetic rearrangements as sources of functional innovations and biodiversity.
Genome Organization; Synteny; Gene Content; Model of Genome Evolution; DCJ