| dc.description | The multigene family of intracellular lipid-binding proteins (iLBP) comprises at least sixteen members that include ten different fatty acid-binding proteins (FABP), four cellular retinol-binding proteins (CRBP) and two cellular retinoic acid-binding proteins (CRABP). All the members of this multigene family are believed to have originated from a single ancestral gene as a result of duplication events. Although the iLBP genes have been intensively investigated in mammals, the physiological functions of their products still remains to be clearly defined and the mechanism of their evolution remains a mystery. I have characterized four members of the iLBP multigene family namely, the intestinal fatty acid-binding protein (I-FABP), basic liver-FABP (Lb-FABP), liver-FABP (L-FABP) and cellular retinoic acid-binding protein II (CRABPII) in zebrafish. The I-FABP, Lb-FABP and CRABPII genes consist of four exons-three introns, similar to that of mammalian iLBPs. The zebrafish L-FABP gene structure is composed of five exons-four introns owing to insertion of an intron in the 5' UTR. All four genes were mapped to zebrafish linkage groups (LG) by radiation hybrid mapping. The I-FABP gene was mapped to LG 1, the Lb-FABP and CRABPII genes to LG 16 and the L-FABP gene to LG 5. Comparative genomic analysis revealed that zebrafish LG 1 has syntenic relationship to human chromosome 4, zebrafish LG 16 to human chromosome 1 and zebrafish LG 5 to human chromosome 2. The dispersal of the iLBP multigene family members in the zebrafish and the human genome suggests that tandem duplication did not play a major role in evolution of the iLBP multigene family. The pattern of expression of the iLBP genes seems to have diverged as compared to their mammalian orthologs. Whole mount in situ hybridization detected I-FABP mRNA in the embryonic zebrafish liver, pancreas and intestine. In adult zebrafish, I-FABP mRNA was detected in the intestine, liver, brain, muscle and testes by RT-PCR analysis. The Lb-FABP mRNA was detected only in the embryonic zebrafish liver but in the adult zebrafish, LbFABP mRNA expression was also found in the testes and intestine. The zebrafish L-FABP transcript was not detected during embryonic development and in the adult zebrafish L-FABP mRNA expression was restricted to the intestine. The zebrafish CRABPII mRNA was widely distributed during embryonic development and in adult tissues. The finned-fish lineage is believed to have undergone a whole genome duplication after divergence from the lobe finned-fish lineage. Therefore, zebrafish may have two genes for each of the mammalian orthologs. Database searches at the National Centre for Biotechnology Information and Wellcome Trust Sanger Institute identified putative duplicated copies of L-FABP (L-FABPb) and CRABPII (CRABPIIb) but not of I-FABP or Lb-FABP genes. Preliminary mRNA expression analysis suggests that subfunctionalization may be responsible for the retention of the duplicated genes in the zebrafish genome. | en_US |
