Ruuskanen Jori O, Xhaard Henri, Marjamäki Anne, Salaneck Erik, Salminen Tiina, Yan Yi-Lin, Postlethwait John H, Johnson Mark S, Larhammar Dan, Scheinin Mika
Department of Pharmacology and Clinical Pharmacology, Turku Graduate School of Biomedical Sciences, University of Turku, Finland.
Mol Biol Evol. 2004 Jan;21(1):14-28. doi: 10.1093/molbev/msg224. Epub 2003 Aug 29.
The alpha(2)-adrenergic receptors (alpha(2)-ARs) belong to the large family of rhodopsinlike G-protein-coupled receptors that share a common structure of seven transmembrane (TM) alpha-helices. The aims of this study were (1) to determine the number of alpha(2)-AR genes in a teleost fish, the zebrafish (Danio rerio), (2) to study the gene duplication events that generated the alpha(2)-AR subtypes, and (3) to study changes in receptor structure that have occurred since the divergence of the mammalian and fish lineages. Here, we report the cloning and chromosomal mapping of fish orthologs for all three mammalian alpha(2)-ARs. In addition, we identified a fourth alpha(2)-AR subtype with two duplicates in zebrafish. Chromosomal mapping showed that the zebrafish alpha(2)-AR genes are located within conserved chromosomal segments, consistent with the origin of the four alpha(2)-AR subtypes by two rounds of chromosome or block duplication before the divergence of the ray fin fish and tetrapod lineages. Thus, the fourth subtype has apparently been present in the common ancestor of vertebrates but has been deleted or is yet to be identified in mammals. The overall percentage identity between the fish and mammalian orthologs is 53% to 67%, and in the TM regions 80% to 87%. These values are clearly lower than what is observed between mammalian orthologs. Still, all of the residues thought to be important for alpha(2)-adrenergic ligand binding are conserved across species and subtypes, and even the most divergent regions of the fish receptors show clear "molecular fingerprints" typical for orthologs of a given subtype.
α₂ - 肾上腺素能受体（α₂ - ARs）属于视紫红质样G蛋白偶联受体大家族，它们具有共同的七跨膜（TM）α - 螺旋结构。本研究的目的是：（1）确定硬骨鱼斑马鱼（Danio rerio）中α₂ - AR基因的数量；（2）研究产生α₂ - AR亚型的基因复制事件；（3）研究自哺乳动物和鱼类谱系分化以来受体结构发生的变化。在此，我们报告了所有三种哺乳动物α₂ - ARs的鱼类直系同源基因的克隆和染色体定位。此外，我们在斑马鱼中鉴定出了具有两个重复拷贝的第四种α₂ - AR亚型。染色体定位表明，斑马鱼α₂ - AR基因位于保守的染色体区段内，这与在辐鳍鱼和四足动物谱系分化之前通过两轮染色体或区段重复产生四种α₂ - AR亚型的起源一致。因此，第四种亚型显然存在于脊椎动物的共同祖先中，但在哺乳动物中已被删除或尚未被鉴定出来。鱼类和哺乳动物直系同源基因之间的总体序列一致性为53%至67%，在跨膜区域为80%至87%。这些值明显低于在哺乳动物直系同源基因之间观察到的值。尽管如此，所有被认为对α₂ - 肾上腺素能配体结合很重要的残基在物种和亚型之间都是保守的，甚至鱼类受体中差异最大的区域也显示出给定亚型直系同源基因典型的清晰“分子指纹”。
