CCL20和CCR6在鼠亚科的进化研究

发布时间：2018-06-19 12:27

本文选题：CCL20基因 + CCR6基因　；参考：《四川农业大学》2015年硕士论文

【摘要】：免疫反应中,趋化因子(chemokines)能够活化特定的趋化因子受体,引起炎症性和非炎症性细胞迁移至感染或受损的位点,从而导致一系列的生理生化反应。其中,趋化因子CCL20与其七跨膜域受体CCR6能发生特异性结合并诱导未成熟树突状细胞(dendritic cell, DC)、效应T细胞或记忆T细胞及B细胞的化学趋向性,且在内稳态、炎症及病理状态下的皮肤和黏膜表面起重要作用。目前,针对CCL20及CCR6的结构和功能,仍有诸多问题有待深入的探讨。免疫相关基因的进化历程和进化机制为我们研究其结构特征及在免疫反应中的功能提供了重要信息。鉴于模式动物,如大鼠和小鼠等在免疫相关研究领域的广泛应用,通过对这些模式动物及其近缘物种中趋化因子CCL20及其受体CCR6的遗传与进化的研究,将有助于我们更为深入的认识其结构与功能的特点。为清晰刻画趋化因子CCL20及其受体CCR6在鼠科动物中的进化历程,本研究测定了鼠亚科(Marinae)动物中多个物种,包括黑线姬鼠(Apodemus agrarius)、中华姬鼠（A. draco)/田鼷鼠(Mus caroli)、锡金小鼠(M. pahari)、黑尾鼠(Niviventer cremoriventer)、波利尼西亚鼠(Rattus exulans)、沼泽鼠(R.fuscipes)、黑鼠(R. rattus)、亚洲家鼠(R. tanezumi), CCL20及CCR6基因编码区序列。结合公共数据库Ensembl中已有的小家鼠(M. musculus)和褐家鼠(R. norvegicus)相应的基因序列,我们系统分析了鼠亚科动物CCL20及CCR6基因的进化情况。主要结果如下：1)鼠亚科9个物种中CCL20及CCR6基因的全长编码序列分别约为290bp和1100bp。CCL20及CCR6基因在鼠亚科以及灵长类动物中保持了较保守的基因结构。2)CCL20基因在鼠亚科中经历适应性进化,共有12个氨基酸位点受到正选择的影响：CCR6基因在这一进化过程中则受到较强的负选择的影响。3)上述正选择位点中有8个位点位于CCL20可能与受体CCR6特异性结合的结构域。该结果提示这些位点可能影响或者参与CCL20蛋白与CCR6的结合。这一重要信息为深入探讨CCL20与其复杂的七次跨膜域受体相互作用的分子机理,及其在免疫反应的调控机理提供了重要信息。本研究基于分子进化角度,对鼠亚科物种中免疫相关基因CCL20及CCR6的进化进行了系统的研究,深入探讨了其进化特征及其影响因素。将有助于我们更好的认识其结构与功能的特点,并为揭示其在免疫反应中的作用提供重要的信息。
[Abstract]:In immune response, chemokinescan activate specific chemokine receptors, causing inflammatory and non-inflammatory cells to migrate to infected or damaged sites, resulting in a series of physiological and biochemical responses. The chemokine CCL20 and its seven transmembrane domain receptor CCR6 can specifically bind and induce the chemotropism of immature dendritic cells, effector T cells or memory T cells and B cells. Inflammatory and pathological skin and mucosal surfaces play an important role. At present, the structure and function of CCL20 and CCR6 still need to be discussed. The evolutionary process and mechanism of immune-related genes provide important information for us to study their structural characteristics and function in immune response. In view of the extensive application of model animals, such as rats and mice, in immune-related research, the inheritance and evolution of the chemokine CCL20 and its receptor CCR6 in these model animals and their related species have been studied. It will help us to understand the characteristics of its structure and function more deeply. In order to clearly describe the evolution of chemokine CCL20 and its receptor CCR6 in rodents, we determined several species in the Marinaeae. They include Apodemus agrariusus, A. draco)/, Mus carolii, M. paharii, Niviventer cremoriventerus, Rattus exulansus, R. fuscipes, R. fuscipes, Rusrattles, R. tanezumiana, CCL20 and CCR6. The evolution of CCL20 and CCR6 genes of Rattus norvegicus and M. musculus in the common database Ensembl were systematically analyzed by combining the corresponding gene sequences of M. musculus and Rhizoma norvegicus. in the common database Ensembl, we systematically analyzed the evolution of CCL20 and CCR6 genes in the subfamily Ensembl. The main results are as follows: (1) the full length coding sequences of CCL20 and CCR6 genes in 9 species of the subfamily mouse are about 290bp and 1100bp.CCL20 and CCR6 genes, respectively. The CCL20 and CCR6 genes maintain a more conserved gene structure in the subfamily mouse and primate. Through adaptive evolution, A total of 12 amino acid loci were affected by positive selection. 3) eight of the positive selection sites were located in the domain of CCL20 binding to the receptor CCR6. These results suggest that these sites may affect or participate in the binding of CCL 20 protein to CCR 6. This important information provides important information for the further study of the molecular mechanism of CCL20 interacting with its complex seven transmembrane domain receptors and its regulatory mechanism in immune response. Based on molecular evolution, the evolution of immune-related genes CCL20 and CCR6 in mouse subfamily was studied systematically, and the evolution characteristics and influencing factors of CCL20 and CCR6 were discussed. It will help us to better understand the characteristics of its structure and function and provide important information for revealing its role in immune response.
【学位授予单位】：四川农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：Q959

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