Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

In 1970, Susumu Ohno proposed the major mechanism that facilitates increasing complexity in the evolution of life is gene duplication. Allan Force and others revisited this idea in the Duplication-Degeneration-Complementation (DDC) model in which duplicated genes are retained in the genome either by subfunctionalization, where the functions of the ancestral gene are sub-divided between the sister duplicate genes, or by neofunctionalization, where one of the duplicates acquires a new function. In this model, both processes for retention of duplicated genes occur by either loss or gain of regulatory elements in the promoters of sister duplicate genes. The common fate of a duplicated gene, however, is nonfunctionalization, the accumulation of deleterious mutations resulting in functional decay. The long-term goal of this research program is to test the hypothesis of the DDC model that duplicated genes are retained in the genome by either sub- or neofunctionalization. The work proposed in this Discovery Grant proposal focusses on the regulation of the duplicated copies of the multigene family of the intracellular lipid-binding protein (iLBP) genes that code for the fatty acid- ( fabp ) and retinol- ( rbp ) and retinoic acid- ( crabp ) binding proteins in zebrafish and other teleost fishes. Zebrafish has been selected for initial studies as teleost genomes compared to other vertebrates are rich in duplicated genes owing to a teleost-specific whole genome duplication (TGD) early in the teleost fish radiation ~230-400 million years ago. In this research program, the complex regulatory mechanisms that control the spatial-temporal expression of a sub-class of the iLBP multigene family, the duplicated fabp genes, will be defined, how the regulatory mechanisms that control their transcription have evolved, and why so many of the duplicated fabp genes have been retained in zebrafish and other teleost genomes compared to the common loss of duplicated genes in fish genomes following the TGD will be determined. Comparative studies will also characterize the peroxisome proliferator (PPAR)-selective, retinoid-receptor (RXR/RAR)-selective, and tissue-specific regulation of the fabp multigene family in zebrafish and the phylogenetically-distant teleost fishes, medaka, spotted green pufferfish, three-spined stickleback and the ancient, pre-TGD teleost, the spotted gar. Analysis of the regulatory mechanisms that control fabp gene transcription in the spotted gar (serving as a representative ancestral fish that did not undergo the TGD) will determine whether the duplicated fabp genes were retained in the teleost genome by either sub- or neofunctionallization. Furthermore, we hope to define the interconnectivity of cis -acting elements in the teleost fabp genes with the fatty acid, PPAR, RXR/RAR signalling pathways.