Evolution of Tissue-specific Expression Following Teleost and Salmonid Whole-Genome Duplication

Abstract

This thesis investigates the evolutionary consequences of two whole-genome duplication (WGD) events in ray-finned fish, the Teleost Genome Duplication (TGD) and the Salmonid-Specific Genome Duplication (Ss4R), through integrative bioinformatics approaches. By analyzing macro-synteny and gene expression data across 13 fish species and outgroup, we identified WGD-derived duplicate genes (ohnologs) and demonstrated that subfunctionalization is the primary mode of expression divergence following WGD. We constructed a comprehensive ohnolog database for teleosts and salmonids, revealing that ohnologs are enriched in dosage-sensitive regulatory pathways and exhibit conserved retention patterns across WGD events, highlighting the importance of dosage balance in genome evolution. Using neural network models, we addressed inconsistencies in previous studies and confirmed that dosage constraints are the key selective force driving ohnolog retention and expression divergence. Furthermore, we developed a multi-tissue expression quantitative trait locus (eQTL) database for zebrafish, demonstrating that ohnologs are significantly enriched in tissue-specific eQTLs. This enrichment aligns with the principles of subfunctionalization, as regulatory variants that do not disrupt expression in dosage-sensitive tissues are selectively retained over evolutionary time. These findings reinforce the dosage-sensitive nature of ohnologs and provide new insights into their regulatory evolution. Overall, this study offers a comprehensive understanding of the impact of WGD on gene retention, expression divergence, and regulatory variation. By comparing two independent WGD events, we provide compelling evidence that dosage constraints are the primary force shaping post-WGD evolution. Our work also establishes the first comprehensive ohnolog dataset for salmonids and expands the teleost ohnolog database, serving as a valuable resource for future research.