On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin.
On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin.
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DOI：
10.3389/fendo.2017.00058
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发表时间：
2017
影响因子：
5.2
通讯作者：
Tuttle M
中科院分区：
文献类型：
--
作者：
Londraville RL;Prokop JW;Duff RJ;Liu Q;Tuttle M
从弗里德曼发现哺乳动物瘦素基因到在鱼类和两栖动物中克隆该基因，已经过去了十多年。自 2005 年以来，基因同线性保守（相对于基因序列同源性）的概念有助于识别数十个物种的瘦素基因，现在我们拥有来自所有主要脊椎动物类别的瘦素基因。这个 LEP（瘦素）、LEPR（瘦素受体）和 LEPROT（内跨膜蛋白）基因数据库允许对大多数脊椎动物类进行蛋白质结构建模、化学计量预测，甚至瘦素功能的功能预测。在这里，我们应用功能基因组学对来自脊椎动物和无脊椎动物的数百种 LEP、LEPR 和 LEPROT 蛋白进行建模。我们鉴定了三种瘦素信号蛋白中每一种的保守结构基序，并证明了果蝇 Dome 蛋白与脊椎动物瘦素受体的保守性。我们首次对内跨膜蛋白结构进行了建模，并鉴定了无脊椎动物基因组中的内跨膜蛋白旁系同源物。最后，我们认为瘦素不是鱼类的脂肪抑制剂，并讨论了鱼类中新兴的基因敲除模型。
Over a decade passed between Friedman’s discovery of the mammalian leptin gene and its cloning in fish and amphibians. Since 2005, the concept of gene synteny conservation (vs. gene sequence homology) was instrumental in identifying leptin genes in dozens of species, and we now have leptin genes from all major classes of vertebrates. This database of LEP (leptin), LEPR (leptin receptor), and LEPROT (endospanin) genes has allowed protein structure modeling, stoichiometry predictions, and even functional predictions of leptin function for most vertebrate classes. Here, we apply functional genomics to model hundreds of LEP, LEPR, and LEPROT proteins from both vertebrates and invertebrates. We identify conserved structural motifs in each of the three leptin signaling proteins and demonstrate Drosophila Dome protein’s conservation with vertebrate leptin receptors. We model endospanin structure for the first time and identify endospanin paralogs in invertebrate genomes. Finally, we argue that leptin is not an adipostat in fishes and discuss emerging knockout models in fishes.