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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Functional characterization and evolutionary history of two aryl hydrocarbon receptor isoforms (AhR1 and AhR2) from avian species.
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Functional characterization and evolutionary history of two aryl hydrocarbon receptor isoforms (AhR1 and AhR2) from avian species.

机译：禽类中两种芳基烃受体亚型（AhR1和AhR2）的功能表征和进化史。

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摘要

Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce various toxic effects through the aryl hydrocarbon receptor (AhR) signaling pathway. Here, we investigated the structural and functional characteristics and molecular evolution of multiple AhRs in black-footed albatross (Phoebastria nigripes) and common cormorant (Phalacrocorax carbo). We report the complementary DNA sequences of two distinct AhRs, designated AhR1 and AhR2, from these species as well as the identification of an AhR2-like gene sequence from the chicken genome database. Phylogenetic analysis reveals that avian AhR1 and AhR2 are orthologous to mammalian AhR1 and fish AhR2, respectively, supporting the hypothesis that an ancestral AhR gene underwent a tandem duplication prior to the divergence of fish and tetrapod lineages. In vitro-expressed AhR1 and AhR2 isoforms from both albatross and cormorant exhibited specific binding to [3H]TCDD, as assessed by velocity sedimentation. An in vitro reporter gene transactivation assayrevealed that both AhR1 and AhR2 are transcriptionally active, but AhR2 appears to have reduced transcriptional efficacy. Hepatic messenger RNA expression level of cormorant AhR1 was greater than that of AhR2. Together, these results suggest that AhR1 is the dominant form of avian AhRs, in contrast to fish, in which AhR2 is the major form. Comparative analysis of AhR diversity and gene synteny among chicken, zebrafish, and human suggests that additional, independent AhR duplications have occurred in the fish and tetrapod lineages following the initial tandem duplication on the ancestral chromosome. The identification and characterization of avian AhR1 and AhR2 provide new insight into the evolution of AhR structure and function in vertebrates.
机译：包括2,3,7,8-四氯二苯并-p-二恶英（TCDD）在内的二恶英通过芳烃受体（AhR）信号传导途径诱导多种毒性作用。在这里，我们研究了黑脚信天翁（Phoebastria nigripes）和普通cor（Phalacrocorax carbo）中多个AhR的结构和功能特征以及分子进化。我们报告了来自这些物种的两个不同的AhRs（称为AhR1和AhR2）的互补DNA序列，以及从鸡基因组数据库中识别了类似AhR2的基因序列。系统发育分析表明，禽AhR1和AhR2分别与哺乳动物AhR1和鱼类AhR2是直系同源的，支持这样的假设：祖先的AhR基因在鱼和四足动物谱系分化之前先进行了串联复制。信天翁和cor在体外表达的AhR1和AhR2亚型​​表现出与[3H] TCDD的特异性结合，通过速度沉降评估。一项体外报道基因反式激活试验表明，AhR1和AhR2均具有转录活性，但AhR2似乎具有降低的转录效力。 AhAhR1的肝信使RNA表达水平高于AhR2。总之，这些结果表明，AhR1是禽类AhRs的主要形式，而鱼类则以AhR2为主要形式。鸡，斑马鱼和人类之间的AhR多样性和基因同源性的比较分析表明，在祖先染色体上进行最初的串联复制后，在鱼类和四足动物谱系中又发生了独立的AhR复制。禽AhR1和AhR2的鉴定和表征为脊椎动物AhR结构和功能的进化提供了新的见识。

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