TISSUE-SPECIFIC DIFFERENTIAL INDUCTION OF DUPLICATED FATTY ACID-BINDING PROTEIN GENES BY THE PEROXISOME PROLIFERATOR, CLOFIBRATE, IN ZEBRAFISH (Danio rerio)

Abstract

Duplicated genes are present in the teleost fish lineage owing to a whole-genome duplication (WGD) event that occured ~ 230-400 million years ago. In the duplication-degeneration-complementation (DDC) model, partitioning of ancestral functions (subfunctionalization) and acquisition of novel functions (neofunctionalization) have been proposed as principal processes for the retention of duplicated genes in the genome. The DDC model was tested by analyzing the differential tissue-specific distribution of transcripts for the duplicated fatty acid-binding protein 10 (fabp10) genes in embryos, larvae and adult zebrafish (Danio rerio). The distribution of zebrafish fabp10a and fabp10b transcripts show a strikingly different tissue-specific pattern leading us to suggest that the zebrafish fabp10 duplicates had been retained in the genome owing to neofunctionalization. In another experiment to test the DDC model, transcriptional regulation of duplicated fabp genes was analyzed in zebrafish fed clofibrate, a peroxisome proliferator-activated receptor (PPAR) agonist. Clofibrate increased the steady-state level of both the duplicated copies of fabp1a/fabp1b.1, and fabp7a/fabp7b mRNA and heteronuclear RNA (hnRNA), but in different tissues of zebrafish. The steady-state level of fabp10a and fabp11a mRNA and hnRNA was elevated in liver of zebrafish, but not for fabp10b and fabp11b. We also investigated the effect of dietary fatty acids (FAs) and clofibrate on the transcriptional regulation of single copy fabp genes, fabp2, fabp3 and fabp6 in zebrafish. The steady-state level of fabp2 transcripts increased in intestine, while fabp3 mRNA increased in liver of zebrafish fed diets differing in FA content. In zebrafish fed clofibrate, fabp3 mRNA in intestine, and fabp6 mRNA in intestine and heart, was elevated. Whether the regulation of fabp gene transcription by clofibrate is controlled either directly or indirectly, the regulatory elements in the zebrafish fabp genes have diverged markedly since the WGD event, thereby supporting the DDC model.