Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family
Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family
复制标题
DOI：
10.1073/pnas.94.25.13743
复制
发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Perera, SA
中科院分区：
文献类型：
--
作者：
Hahn, ME;Karchner, SI;Perera, SA
芳香烃受体(AHR)是一种配体激活的转录因子，通过2，3，7，8-四氯二苯并-对二恶英(TCDD)等卤代芳烃引起基因表达改变和毒性作用。AHR属于碱性螺旋-环-螺旋/Per-Arnt-Sim(bHLH-PAS)转录调节蛋白家族，其成员在发育、昼夜节律性和环境动态平衡中发挥关键作用；然而，AHR的正常细胞功能尚不清楚。作为了解AHR功能和进化起源的系统发育方法的一部分，我们对几种早期脊椎动物AHR的PAS同源结构域进行了测序，并对这些AHR的氨基酸序列与哺乳动物AHR和PAS家族其他24个成员进行了系统发育分析。AHR序列在硬骨鱼(千里鱼Fundulus Heterocltes)、两个弹棘鱼物种(溜鱼Raja erinacea和狗角鱼Mustelus canis)和一种无颌鱼(七鳃鳗Petromyzon marinus)中被鉴定。在Fundulus和Mustelus中都发现了两个可能的AHR基因，命名为AHR1和AHR2。系统发育分析表明，这两个物种的AHR2基因是同源的，这表明AHR基因在脊椎动物进化的早期就发生了复制，其他脊椎动物中可能存在多个AHR基因。数据库搜索和系统发育分析在线虫秀丽线虫中鉴定了四种推定的PAS蛋白，包括可能的AHR和Arnt同源物。对Pas基因家族的系统发育分析表明，包含无脊椎动物和脊椎动物Pas家族成员的不同分支；后者包括我们认为在脊椎动物进化早期由于基因复制而产生的平行序列。总体而言，我们的分析表明AHR是存在于所有现存脊椎动物群体中的一种古老的系统发育蛋白(可能存在无脊椎动物同源物)，从而为二恶英毒性和AHR功能的研究提供了一个进化的视角。
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor through which halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) cause altered gene expression and toxicity. The AHR belongs to the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcriptional regulatory proteins, whose members play key roles in development, circadian rhythmicity, and environmental homeostasis; however, the normal cellular function of the AHR is not yet known. As part of a phylogenetic approach to understanding the function and evolutionary origin of the AHR, we sequenced the PAS homology domain of AHRs from several species of early vertebrates and performed phylogenetic analyses of these AHR amino acid sequences in relation to mammalian AHRs and 24 other members of the PAS family. AHR sequences were identified in a teleost (the killifish Fundulus heteroclitus), two elasmobranch species (the skate Raja erinacea and the dogfish Mustelus canis), and a jawless fish (the lamprey Petromyzon marinus). Two putative AHR genes, designated AHR1 and AHR2, were found both in Fundulus and Mustelus. Phylogenetic analyses indicate that the AHR2 genes in these two species are orthologous, suggesting that an AHR gene duplication occurred early in vertebrate evolution and that multiple AHR genes may be present in other vertebrates. Database searches and phylogenetic analyses identified four putative PAS proteins in the nematode Caenorhabditis elegans, including possible AHR and ARNT homologs. Phylogenetic analysis of the PAS gene family reveals distinct clades containing both invertebrate and vertebrate PAS family members; the latter include paralogous sequences that we propose have arisen by gene duplication early in vertebrate evolution. Overall, our analyses indicate that the AHR is a phylogenetically ancient protein present in all living vertebrate groups (with a possible invertebrate homolog), thus providing an evolutionary perspective to the study of dioxin toxicity and AHR function.