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The CYP1D subfamily of genes in mammals and other vertebrates
Authors:Yusuke K Kawai  Yoshinori Ikenaka  Shoichi Fujita  Mayumi Ishizuka
Institution:1. Laboratory of Toxicology, Department of Environmental Veterinary Science, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, 060-0818, Japan
Abstract:Members of the cytochrome P450 family 1 (CYP1s) are involved in the detoxification and bioactivation of numerous environmental pollutants and phytochemicals such as polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and flavonoids. The vertebrate CYP1 gene comprises four subfamilies: CYP1A, CYP1B, CYP1C, and CYP1D. Recently, the CYP1D gene was identified in fish, and subsequently in the platypus. These findings indicate the possibility that all vertebrates have a functional CYP1D subfamily. However, there is no information on the mammalian CYP1D gene. In this study we investigated the genomic location of CYP1D genes in mammals and other vertebrates in silico. We also performed phylogenetic analysis and calculated the identities and similarities of CYP1D sequences. The data from synteny and phylogenetic analyses of CYP1D genes demonstrated the evolutionary history of the CYP1 gene family. The results suggested that CYP1D became a nonfunctional pseudogene in human and bovine species; however, several other mammals possess functional CYP1D genes. The promoter regions of CYP1D genes were also examined. Unlike other CYP1 isoforms, few xenobiotic responsive element (XRE)-like sequences were found upstream of the CYP1D genes. Analysis of mammalian CYP1Ds also provided new insight into the relationship between CYP1 genes and the aryl hydrocarbon receptor.
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