Porcine taurochenodeoxycholic acid 6α-hydroxylase, cytochrome P450 4A21 (CYP4A21), differs from other members of the CYP4A subfamily in terms of structural features and catalytic activity. CYP4A21 participates in the formation of hyocholic acid, a species-specific primary bile acid in the pig. The CYP4A21 gene was investigated and found to be approx. 13 kb in size and split into 12 exons. The intron–exon organization of the CYP4A21 gene corresponds to that of CYP4A fatty acid hydroxylase genes in other species. Comparison with a genomic segment of a pig CYP4A fatty acid hydroxylase gene (CYP4A24) revealed a sequence identity with CYP4A21 that extends beyond the exons, indicating a common origin by gene duplication. A pronounced sequence identity was found also within the proximal 5´-flanking regions, whereas the patterns of mRNA expression of CYP4A21 and CYP4A fatty acid hydroxylases in pig liver differ. Sequence comparison aiming to elucidate the origin of the unique features of CYP4A21 revealed a region of decreased sequence identity from exon 6 to exon 8, strongly suggesting that gene conversion could have contributed to the evolution of CYP4A21.
Abbreviations used: Sp1, specificity protein 1; YY1, Yin-Yang-1.
The compiled genomic sequences of CYP4A21 and CYP4A24, from exon 2 to 12 and from exon 2 to intron 11, have been submitted to the EMBL database under accession numbers AJ586618 and AJ586619 respectively. The sequences of the 5´-flanking regions and adjacent nucleotides in exon 1 of the CYP4A21 and CYP4A24 genes have been deposited in the EMBL database under accession numbers AJ586859 and AJ586860, respectively.