Cytochrome P450 1 Genes in Birds: Evolutionary Relationships and Transcription Profiles in Chicken and Japanese Quail Embryos

Abstract

BackgroundCytochrome P450 1 (CYP1) genes are biomarkers for aryl hydrocarbon receptor (AHR) agonists and may be involved in some of their toxic effects. CYP1s other than the CYP1As are poorly studied in birds. Here we characterize avian CYP1B and CYP1C genes and the expression of the identified CYP1 genes and AHR1, comparing basal and induced levels in chicken and quail embryos.Methodology/Principal FindingsWe cloned cDNAs of chicken CYP1C1 and quail CYP1B1 and AHR1. CYP1Cs occur in several bird genomes, but we found no CYP1C gene in quail. The CYP1C genomic region is highly conserved among vertebrates. This region also shares some synteny with the CYP1B region, consistent with CYP1B and CYP1C genes deriving from duplication of a common ancestor gene. Real-time RT-PCR analyses revealed similar tissue distribution patterns for CYP1A4, CYP1A5, CYP1B1, and AHR1 mRNA in chicken and quail embryos, with the highest basal expression of the CYP1As in liver, and of CYP1B1 in eye, brain, and heart. Chicken CYP1C1 mRNA levels were appreciable in eye and heart but relatively low in other organs. Basal transcript levels of the CYP1As were higher in quail than in chicken, while CYP1B1 levels were similar in the two species. 3,3′,4,5,5′-Pentachlorobiphenyl induced all CYP1s in chicken; in quail a 1000-fold higher dose induced the CYP1As, but not CYP1B1.Conclusions/SignificanceThe apparent absence of CYP1C1 in quail, and weak expression and induction of CYP1C1 in chicken suggest that CYP1Cs have diminishing roles in tetrapods; similar tissue expression suggests that such roles may be met by CYP1B1. Tissue distribution of CYP1B and CYP1C transcripts in birds resembles that previously found in zebrafish, suggesting that these genes serve similar functions in diverse vertebrates. Determining CYP1 catalytic functions in different species should indicate the evolving roles of these duplicated genes in physiological and toxicological processes.

Functional characterization of zebrafish cytochrome P450 1 family proteins expressed in yeast

“…However, the formation of a novel testosterone metabolite suggests that there could be unrecognized biological functions of CYP1D1. It also may be that the biological importance of CYP1D1 is diminishing over evolution, suggested by the loss or pseudogenization of the CYP1D1 gene in some vertebrates [20,63]. …”

“…Mammals express three CYP1 genes in two subfamilies, CYP1A (genes CYP1A1 and CYP1A2) and CYP1B (gene CYP1B1), all three of which are inducible by aryl hydrocarbon receptor (AHR) agonists [14]. Other vertebrates (fish, amphibians, birds) have four CYP1 subfamilies, CYP1A and CYP1B, as well as the more recently discovered CYP1C and CYP1D [15–20]. Teleost fish such as zebrafish typically have five CYP1 genes, CYP1A, CYP1B1, CYP1C1, CYP1C2 and CYP1D1 [16,17].…”

Avian Cytochrome P450 (CYP) 1-3 Family Genes: Isoforms, Evolutionary Relationships, and mRNA Expression in Chicken Liver

“…Recently, enzymatic characteristics and phylogenetic relationships within each family have been examined for the chicken CYP isoforms, i.e., CYP1, CYP2C, CYP2D49, and CYP3A37 [7], [8] [9], [10], [11]. However, the xenobiotic-metabolizing CYP genes in avian species have not been completely elucidated, and the importance of each isoform has not been evaluated in comparison with other isoforms.…”

Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery

“…Birds have two CYP1A genes, CYP1A4 and 1A5 , which are orthologous to mammalian CYP1A1 and 1A2 [ 59 ]. CYP1C members are found in several bird genomes, but not in quail [ 60 ]. The CYP1C genomic region is highly conserved among vertebrates.…”