G蛋白偶联受体（GPCR）广泛参与哺乳动物生长和发育等多种生命活动以及内分泌和代谢等多种生理过程。GPCR最大特征是其七次跨膜组成一个配体结合口袋，受配体在结构与功能上密切相关，在进化上也相互影响。目前对GPCR受体配体的分子进化研究多聚焦于受配体在不同物种中的协同进化，而对于GPCR受配体关系起源研究却较为匮乏，且尚无明确实例。这里，我们提出GPCR受配体关系起源的三种模型：配体适应性进化，受体适应性进化和受配体共适应性进化。并以一个灵长类新起源的年轻配体基因-CCL18多肽为例，我们引入蛋白三维结构模拟技术与传统分子进化方法结合起来分析选择压力位点的功能，同时配合多种功能实验验证其突变体功能，阐明CCL18通过适应性进化最终结合其在脊椎动物中广泛存在且保守的受体-PITPNM3。我们的研究为GPCR受体配体关系的起源模型提供第一个清楚的实例，进而为细胞内受配体互作的分子进化提供新思路。

G protein-coupled receptors (GPCRs) in peptide hormone family sense molecules outside the cell and activate inside G protein signal transduction pathways and, ultimately, have an important effect on mammalian growth and development. The ligands of GPCRs typically bind within their 7 transmembrane domains and GPCR are evolutionarily related to their cognate ligands with 7 transmembrane domains. Up to now, the co-evolution of GPCR-ligands in diverse species attracts great interests. However, Origination model of GPCR-ligand relationship, which is important for functional study of GPCR, was not illuminated. Here, we propose three models of origination model of GPCR-ligand relationship: adaptive evolved ligand, adaptive evolved receptor and adaptive evolved receptor and ligand. Moreover, we studied CCL18, a primate derived chemokine ligand as a case study of adaptive evolved ligand model, with the protein 3D structure simulation technology and classic molecular evolution analysis. Our study will provide new perspectives in molecular evolution of all plasma membrane receptor and ligands.