Larhammar D, Salaneck E
Department of Neuroscience, Unit of Pharmacology, Box 593 Uppsala University, SE-75124 Uppsala, Sweden.
Neuropeptides. 2004 Aug;38(4):141-51. doi: 10.1016/j.npep.2004.06.002.
The neuropeptide Y (NPY) system consists in mammals of three peptides and 4-5 G-protein-coupled receptors called Y receptors that are involved in a variety of physiological functions such as appetite regulation, circadian rhythm and anxiety. Both the receptor family and the peptide family display unexpected evolutionary complexity and flexibility as shown by information from different classes of vertebrates. The vertebrate ancestor most likely had a single peptide gene and three Y receptor genes, the progenitors of the Y1, Y2 and Y5 subfamilies. The receptor genes were probably located in the same chromosomal segment. Additional gene copies arose through the chromosome quadruplication that took place before the emergence of jawed vertebrates (gnathostomes) whereupon differential losses of the gene copies ensued. The inferred ancestral gnathostome gene repertoire most likely consisted of two peptide genes, NPY and PYY, and no less than seven Y receptor genes: four Y1-like (Y1, Y4/a, Y6, and Yb), two Y2-like (Y2 and Y7), and a single Y5 gene. Whereas additional peptide genes have arisen in various lineages, the most common trend among the Y receptor genes has been further losses. Mammals have lost Yb and Y7 (the latter still exists in frogs) and Y6 is a pseudogene in several mammalian species but appears to be still functional in some. One challenge is to find out if mammals have been deprived of any functions through these gene losses. Teleost fishes like zebrafish and pufferfish, on the other hand, have lost the two major appetite-stimulating receptors Y1 and Y5. Nevertheless, teleost fishes seem to respond to NPY with increased feeding why some other subtype probably mediates this effect. Another challenge is to deduce how Y2 and Y4 came to evolve an inhibitory effect on appetite. Changes in anatomical distribution of receptor expression may have played an important part in such functional switching along with changes in receptor structures and ligand preferences.
神经肽Y（NPY）系统在哺乳动物中由三种肽和4 - 5种称为Y受体的G蛋白偶联受体组成，这些受体参与多种生理功能，如食欲调节、昼夜节律和焦虑。正如来自不同类脊椎动物的信息所示，受体家族和肽家族都表现出意想不到的进化复杂性和灵活性。脊椎动物的祖先很可能有一个单一的肽基因和三个Y受体基因，即Y1、Y2和Y5亚家族的祖基因。这些受体基因可能位于同一染色体片段上。在有颌脊椎动物（gnathostomes）出现之前发生的染色体四倍化产生了额外的基因拷贝，随后基因拷贝出现了差异性丢失。推断的有颌脊椎动物祖先基因库很可能由两个肽基因，即NPY和PYY，以及不少于七个Y受体基因组成：四个Y1样基因（Y1、Y4/a、Y6和Yb），两个Y2样基因（Y2和Y7），以及一个单一的Y5基因。虽然在各种谱系中出现了额外的肽基因，但Y受体基因中最常见的趋势是进一步丢失。哺乳动物已经失去了Yb和Y7（后者在青蛙中仍然存在），并且Y6在几种哺乳动物物种中是假基因，但在某些物种中似乎仍然具有功能。一个挑战是弄清楚哺乳动物是否因这些基因丢失而丧失了任何功能。另一方面，像斑马鱼和河豚这样的硬骨鱼已经失去了两种主要的刺激食欲的受体Y1和Y5。然而，硬骨鱼似乎对NPY有反应，摄食量增加，这是因为其他一些亚型可能介导了这种效应。另一个挑战是推断Y2和Y4是如何进化出对食欲的抑制作用的。受体表达的解剖分布变化可能在这种功能转换中起到了重要作用，同时受体结构和配体偏好也发生了变化。
