Londraville Richard Lyle, Prokop Jeremy W, Duff Robert Joel, Liu Qin, Tuttle Matthew
Program in Integrative Bioscience, Department of Biology, University of Akron, Akron, OH, USA.
Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
Front Endocrinol (Lausanne). 2017 Apr 10;8:58. doi: 10.3389/fendo.2017.00058. eCollection 2017.
Over a decade passed between Friedman's discovery of the mammalian leptin gene (1) and its cloning in fish (2) and amphibians (3). 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 (leptin), (leptin receptor), and (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 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.
从弗里德曼发现哺乳动物瘦素基因（1）到其在鱼类（2）和两栖动物中的克隆（3），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）的概念有助于在数十个物种中鉴定瘦素基因，现在我们已经拥有了所有主要脊椎动物类别的瘦素基因。这个包含（瘦素）、（瘦素受体）和（内体素）基因的数据库使得对大多数脊椎动物类别的瘦素功能进行蛋白质结构建模、化学计量预测甚至功能预测成为可能。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。我们在三种瘦素信号蛋白中的每一种中鉴定出保守的结构基序，并证明穹顶蛋白与脊椎动物瘦素受体的保守性。我们首次对内体素结构进行建模，并在无脊椎动物基因组中鉴定出内体素旁系同源物。最后，我们认为瘦素在鱼类中不是一种脂肪稳态因子，并讨论了鱼类中新兴的基因敲除模型。
