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灵长类苦味受体16 号基因（ T2R16 T2R16）的功能与进化研究
文献类型：学位论文
| 作者 | 范飞 |
| 学位类别 | 硕士 |
| 答辩日期 | 2013-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 施鹏 |
| 关键词 | T2R16 正选择 水杨苷 功能分化 点突变 |
| 其他题名 | Evolutionary and Functional study of T2R16 in primates |
| 学位专业 | 遗传学 |
| 中文摘要 | 在哺乳动物中，苦味受体是由苦味受体基因（T2R）家族编码的七次跨膜G蛋白偶联受体（GPCR）。苦味感觉可以避免动物摄入有毒的物质，因为自然界中很多有毒的物质都是苦的，是一种有效的防御机制。苦味受体16号基因（T2R16）是苦味受体基因家族中的一员，是第一个被鉴定的能被天然的苦味物质激活的苦味受体。研究显示T2R16在人中受到了正选择作用。并且该受体在灵长类中功能有不同程度的分化，其中人、黑猩猩、叶猴和猕猴的T2R16受体都能不同程度的识别相应的苦味配体，但绒猴的该受体却不能识别这些苦味配体。这些结果提示T2R16在灵长类进化过程中可能存在着某个阶段的适应性进化，而与之前报道的灵长类嗅觉、味觉和听觉等都逐步退化相矛盾。我们主要研究灵长类T2R16受体的进化和功能，试图揭示该基因是否在灵长类进化过程中发生了适应性进化，加深我们对灵长类苦味受体基因演化的理解。 本文通过体外功能实验对8个灵长类物种以及人猿超科、狭鼻猴、新大陆猴和类人猿下目4个祖先状态的T2R16受体进行功能分析，结合24个灵长类的T2R16的进化分析，发现T2R16在灵长类进化过程中至少发生了3次适应性进化事件。这些适应性进化事件分别发生在类人猿下目共同祖先、狭鼻猴共同祖先和人群中。这是首次在一对一直系同源基因的水平上揭示了T2R16在灵长类中3次适应性进化。 为了进一步揭示T2R16适应性进化的分子机制，我们首先基于序列分析找出类人猿下目共同祖先和狭鼻猴共同祖先序列的保守氨基酸，在类人猿下目和狭鼻猴共同祖先中分别有13个和5个保守氨基酸。然后，我们通过点突变功能实验发现T82K、I211M、V239M这3个氨基酸的突变体（mutant），显著地降低了T2R16受体对苦味物质的检测能力。提示着我们，在狭鼻猴共同祖先时期，可能由于K82T、M211I和M239V三个氨基酸位点的突变增加了在该阶段T2R16受体对苦味物质的检测能力，该结果对全面的揭示T2R16在灵长类中的适应性进化机制提供了可行的思路和方法。 |
| 英文摘要 | In mammals, the bitter receptors are encoded by the bitter taste receptor gene (T2R) family, and they are seven transmembrane G protein coupled receptors (GPCR). Bitter taste is an effective defense mechanism that can avoid animals eating toxic substance since most of them are bitter. Bitter taste receptor gene 16 (T2R16) is a member of the bitter taste receptor gene family, which is the first identified receptor can be activated by natural bitterness substances. Research shows that T2R16 in human is under positive selection. And the function of T2R16 receptors have different degree of differentiation in primates, with human, chimpanzees, langur and macaques T2R16 receptors can recognize their corresponding ligands to different extent, however, the marmoset cannot recognize these bitter taste receptors ligands. These results implies that T2R16 may under adaptive evolution in the course of primate evolution, contradict with previously hypothesis that smell, taste and hearing abilities in primates were gradually degraded. Our main research focus is the evolution and function of the primate T2R16 receptors, tries to reveal whether the gene is under adaptive evolution in primates, deepen our understanding of evolution of bitter taste receptors in primates. Based on the functional analysis of T2R16 receptors in 8 primate species and 4 common ancestors (Hominoidea, Catarrhini, Platyrrhini and Simiiformes), combined with the evolution analysis of them in 24 primates, at least three adaptive evolutionary events were identified during primate evolution. These adaptive evolutionary events happened at the common ancestor of Simiiformes, common ancestor of Catarrhini and the human population. In this study, for the first time we revealed that T2R16 are under adaptive evolution in primates from one-to-one orthologous gene level. In order to further reveal the T2R16 molecular mechanisms of adaptive evolution, we firstly identify the conservative amino acid at the Simiiformes common ancestor and Catarrhini common ancestor through sequence comparison, which are 13 and 5 respectively. We then discovered that mutants at amino acids T82K I211M V239M significantly reduce the bitter substances detection ability of T2R16 receptors. This result indicates that at common ancestor of narrow nasal monkey the bitter detection ability may be increased due to the mutation of three amino acids, K82T M211I and M239V. This study has shed light on the ideas and methods of the T2R16 adaptive evolution analysis in primates. |
| 语种 | 中文 |
| 公开日期 | 2013-06-06 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7454]  |
| 专题 | 昆明动物研究所_进化与功能基因组学 |
| 推荐引用方式 GB/T 7714 | 范飞. 灵长类苦味受体16 号基因（ T2R16 T2R16）的功能与进化研究[D]. 北京. 中国科学院研究生院. 2013. |
入库方式： OAI收割
来源：昆明动物研究所
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