Closely Related Genes Encode Developmental and Tissue Isoforms of Porcine Cytochrome P450 Aromatase

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Abstract
We examined the chromosomal basis for the synthesis of tissue (ovary, endometrium/placenta, and peri-implantation blastocyst) isoforms of cytochrome P450 aromatase in the pig. DNA fragments derived from three distinct porcine aromatase chromosomal genes were cloned and characterized. The porcine type III aromatase gene encoding the blastocyst aromatase isoform was found to consist of nine coding exons and two mutually exclusive, 5' untranslated exons (designated E1A and E1B), collectively spanning 30 kb or more. The porcine type II aromatase gene, encoding the endometrial/placental aromatase isoform, was identified by cloning of a genomic DNA fragment spanning the corresponding exons 7, 8, and 9. The DNA inserts of two other phage clones encompassed exons 2, 3, and 4 of a third chromosomal gene (type I) encoding the ovarian aromatase isoform. All intron-exon junctions in these genomic fragments were found to be identical in relative positions to those of the single-copy human aromatase gene. Comparisons of cDNA and genomic sequences indicated that nucleotide sequence variation was not uniform across the corresponding exons of these genes and that the corresponding intronic sequences were conserved. The type II and type III aromatase genes were localized to the same regional location (q16-17) on swine chromosome 1, which is homologous to the human chromosome 15 region (q21.1) in which the human aromatase gene resides. Results demonstrate that the three aromatase genes characterized in the present study appear to be similar in their overall structural organization and most likely are clustered, which could have resulted from at least two independent gene duplication events. The presence of multiple aromatase genes constitutes a newly described mechanism by which aromatase enzyme biosynthesis and functional activity can be regulated in a tissue and temporal fashion and serves to highlight further the complexity of aromatase gene expression in mammals. Moreover, the presence of a unique aromatase gene that is highly expressed in pig blastocysts may constitute a paradigm for other mammals (e.g., equids, rabbit, hamster) whose peri-implantation blastocysts are estrogenic.