Cytochrome p450 1 genes in early deuterostomes (tunicates and sea urchins) and vertebrates (chicken and frog): Origin and diversification of the CYP1 gene family
Cytochrome p450 1 genes in early deuterostomes (tunicates and sea urchins) and vertebrates (chicken and frog): Origin and diversification of the CYP1 gene family
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DOI：
10.1093/molbev/msm200
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发表时间：
2007-12-01
影响因子：
10.7
通讯作者：
Stegeman, John J.
中科院分区：
文献类型：
--
作者：
Goldstone, Jared V.;Goldstone, Heather M. H.;Stegeman, John J.
细胞色素P450家族1 （CYP1）蛋白在许多毒理学过程中起重要作用。CYP1A和CYP1B基因在哺乳动物中是众所周知的，但CYP1家族作为一个整体的进化史是模糊的；这段历史可能为了解CYP1酶的内源性功能提供了线索。在这里，我们在早期后口动物（被囊动物和棘皮动物）中发现了CYP1样基因，在脊椎动物（鸡、鸡和青蛙、热带爪蟾）中发现了几个新的CYP1基因。利用脊椎动物CYP1A和CYP1B蛋白序列生成的隐马尔可夫模型（hmm），鉴定了被囊动物Ciona ninterinalis基因组中5个潜在的CYP1同源物。对大肠杆菌基因进行了克隆和测序，证实了预测的序列。这些基因中有4个同源基因在乔娜基因组中被发现。贝叶斯系统发育分析将被囊基因归为CYP1家族，暂时分为两个新的亚家族，CYP1E和CYP1F，分别属于CYP1A和CYP1B/1C分支。贝叶斯和最大似然分析预测了被囊动物和脊椎动物CYP1s之间的功能差异，并且发现在CYP底物识别位点的区域在被囊动物和脊椎动物之间的位置特异性替代率存在显着差异。随后，在棘皮动物刺胆基因组中发现了10个cyp1样基因。一些被囊动物和棘皮动物的cyp1样基因在发育过程中表达。典型的异种反应元件存在于大多数被囊动物和海胆CYP1s的上游基因组序列中，并且预测这两个群体都具有芳烃受体（AHR），这表明AHR可能与这些CYPs有调控联系。CYP1家族经历了多轮基因复制，随后是功能分化，在哺乳动物中至少丢失了一个基因。本研究为CYP1基因的起源和进化提供了新的认识。
Cytochrome P450 family 1 (CYP1) proteins are important in a large number of toxicological processes. CYP1A and CYP1B genes are well known in mammals, but the evolutionary history of the CYP1 family as a whole is obscure; that history may provide insight into endogenous functions of CYP1 enzymes. Here, we identify CYP1-like genes in early deuterostomes (tunicates and echinoderms), and several new CYP1 genes in vertebrates (chicken, Gallus gallus and frog, Xenopus tropicalis). Profile hidden Markov models (HMMs) generated from vertebrate CYP1A and CYP1B protein sequences were used to identify 5 potential CYP1 homologs in the tunicate Ciona intestinalis genome. The C. intestinalis genes were cloned and sequenced, confirming the predicted sequences. Orthologs of 4 of these genes were found in the Ciona savignyi genome. Bayesian phylogenetic analyses group the tunicate genes in the CYP1 family, provisionally in 2 new subfamilies, CYP1E and CYP1F, which fall in the CYP1A and CYP1B/1C clades. Bayesian and maximum likelihood analyses predict functional divergence between the tunicate and vertebrate CYP1s, and regions within CYP substrate recognition sites were found to differ significantly in position-specific substitution rates between tunicates and vertebrates. Subsequently, 10 CYP1-like genes were found in the echinoderm Strongylocentrotus purpuratus ( sea urchin) genome. Several of the tunicate and echinoderm CYP1-like genes are expressed during development. Canonical xenobiotic response elements are present in the upstream genomic sequences of most tunicate and sea urchin CYP1s, and both groups are predicted to possess an aryl hydrocarbon receptor (AHR), suggesting possible regulatory linkage of AHR and these CYPs. The CYP1 family has undergone multiple rounds of gene duplication followed by functional divergence, with at least one gene lost in mammals. This study provides new insight into the origin and evolution of CYP1 genes.