Phylogenetic Analysis of the Cytochrome P450 3 (CYP3) Gene Family

Abstract

Cytochrome P450 genes (CYP) constitute a superfamily with members known from the Bacteria, Archaea, and Eukarya. The CYP3 gene family includes the CYP3A and CYP3B subfamilies. Members of the CYP3A subfamily represent the dominant CYP forms expressed in the digestive and respiratory tracts of vertebrates. The CYP3A enzymes metabolize a wide variety of chemically diverse lipophilic organic compounds. To understand vertebrate CYP3 diversity better, we determined the killifish (Fundulus heteroclitus) CYP3A30 and CYP3A56 and the ball python (Python regius) CYP3A42 sequences. We performed phylogenetic analyses of 45 vertebrate CYP3 amino acid sequences using a Bayesian approach. Our analyses indicate that teleost, diapsid, and mammalian CYP3A genes have undergone independent diversification and that the ancestral vertebrate genome contained a single CYP3A gene. Most CYP3A diversity is the product of recent gene duplication events. There is strong support for placement of the guinea pig CYP3A genes within the rodent CYP3A diversification. The rat, mouse, and hamster CYP3A genes are mixed among several rodent CYP3A subclades, indicative of a complex history involving speciation and gene duplication.

Cytochrome P450 1A1 and aromatase (CYP19) in cetaceans : enzyme expression and relationship to contaminant exposure

“…The functional differences between mamals and fish aromatases were marginal (8.. 0.5, Table 4) and the distrbution of functionally diverging residues was random across the protein (data not shown). This is in strong contrast to the CYP3 famly where the functional differences between taxa were very strong and large clustering of divergent residues enabled the identification of regions of the protein that were distinct (McArhur et al 2003). Since DIVERGE requires at least four sequences per grouping, it was impossible to test the functional divergence within the pig aromatases specifically.…”

“…Alignment and analysis were performed as described elsewhere (McArhur et al 2003). In brief, sequence alignment was performed using ClustalX 1.81 (Thompson et al 1997), with manual correction by eye.…”

α-Tocopherol Status and Altered Expression of α-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models

“…Rat CYP3A2 is a member of the CYP3A superfamily, and is approximately 70% identical to human CYP3A4 (45). The CYP3A superfamily comprises multiple members with multiple functions.…”

A microtiter-plate-based cytochrome P450 3A activity assay in fish cell lines

“…Induction of CYP3A expression by rifampicin and dexamethasone has been shown to occur in fish [7]. Cytochrome P450 3A was identified in several teleost species (e.g., CYP3A27 and CYP3A45 in rainbow trout [5,8], CYP3A38 and CYP3A40 in medaka [9,10], CYP3A30 and CYP3A56 in killifish [11], and CYP3A65 in Danio rerio [7]). …”