哺乳动物适应性进化的分子机制探讨——若味受体基因和犁鼻器受体1基因的研究
文献类型：学位论文
| 作者 | 施鹏 |
| 学位类别 | 博士 |
| 答辩日期 | 2004-07 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 张亚平 |
| 关键词 | 适应进化 苦味受体（T2R） 犁鼻器受体1（V1R） 基因重复 正选择 |
| 其他题名 | Molecular Mechanism of Adaptive Evolution in Mammals: Bitter Taste Receptor Gene and Vomeronasal Receptor 1 Gene Analyses |
| 中文摘要 | 动物的适应进化是生物学研究的最基本的问题之一。虽然，人们早从形态学上研究了动物的适应现象，但是对适应的遗传学机制知之甚少。动物感觉系统对周围环境的适应是动物适应进化中的一个关键问题。因此，我们选取了动物感觉系统中苦味受体基因家族（T2R）和犁鼻器受体1基因家族（VIR）为研究对象，对哺乳动物适应性进化的分子机制进行探讨。通过生物信息学和分子生物学手段相结合，我们在哺乳动物6个目共16个物种中获得了157个的苦味味觉受体基因，并对这些TZR基因的系统发育关系进行分析，结果显示哺乳动物的TZR基因家族经历了"生一和一灭"的进化模式，即频繁的基因重复和假基因化。另外，结果还显示这些基因可以被分为3个主要类群，分别命名为A，B和C。有趣的是，B和C类群的基因在所研究的物种间普遍是一对一的直系同源的，而A类群基因则显示了种属或世系特异性。有可能B和C类群的基因是识别哺乳动物共同的苦味物质所必需的，而A类群基因则是用于识别具有种属特异性的苦味物质。这个分析还揭示了在系统发育关系上近相关的基因在它们的染色体位置上也是靠近的，这证明了串联重复是新的TZR基因产生的主要方式。此外，通过核昔酸的异义替换数和同义替换数的比较显示不同物种新近产生的基因所编码的受体蛋白在膜外区的异义替换数显著地大于同义替换数，提示着这些通过基因重复产生的新基因受到了正选择的作用。在自然界中，许多的天然有毒物质一般都是苦的，因此，我们推测哺乳动物TZR基因的分"化选择是为了使其在探索新的生活环境和寻找新食物时能够辨别出更多不同的有毒物质，更好地适应新环境。此外，我们还研究了苦味受体基因和甜味／鲜味受体基因的进化途径。结果显示苦味受体基因和甜味／鲜味受体基因在进化上具有远相关，并具有不同的进化途径，提示着这可能是导致了这些受体基因具有不同功能，传导不同味觉的原因。犁鼻受体噬因家族（VIR）是哺乳动物的信息素受体。应用生物信息学手，我们从大鼠和小鼠的基因组中分别得到了152和115个VIR基因。大鼠VIR基因家族包含11个亚家族，其中10个是与小鼠共享的，而M家族是大鼠特有的；另夕卜大鼠缺少了H和I亚家族，而这两个亚家族存在于小鼠的基因组中。系统发育关系分析发现，"生一和一灭"进化模式也在V1R基因的进化过程中占了主导地位。所有检测到的亚家族都出现于啮齿目和灵长目分歧之后，这说明V1R基因的多样性反映了这一基因家族在啮齿目内基因重复、丢失，基因漂变及自然选择等作用的动态过程。我们的分析还表明大部分不同亚家族下的基因簇爆发的时间接近于大、小鼠分歧的时间。此外，用最大似然法分析的结果表明在这些基因簇中异义替换和同义替换的比值远大于1，揭示了正选择在这些基因的分化过程的作用。一般认为V1R在动物识别信息素过程中起重要的作用，因此我们推测V1R基因的适应性进化是为了使不同的哺乳动物能够识别不同的、复杂的信息素。 |
| 英文摘要 | Adaptive evolution in animals is one of fundamental issues in biology. Although evolutionary adaptations of organisms to their environments are often investigated at the morphological level, little is understood on the molecular genetic base. An essential question in this field was the adaptation of animal sensory system to the surrounding environments. Therefore, the bitter taste receptor (T2R) and the vomeronasal receptor 1 (V1R) gene families belonging to the sensory system were utilized here to explore the molecular mechanism of adaptive evolution in mammals. In this thesis, we identified a total of 157 T2R genes from 16 mammalian species of six orders using the bioinformatics and molecular biology methods. The phylogenetic analysis of these T2R genes revealed that the birth-and-death process, characterized by frequent gene duplication and occasional gene deactivation, is the dominant pattern observed in T2R evolution. In addition, phylogenetic results also suggest that these genes can be classified into three main groups, designated A, B, and C. Interestingly, one-to-one gene orthology is found common to group B and C genes while group A genes show a pattern of species- or lineage-specific duplication. It is possible that group B and C genes are necessary for detecting bitter tastants common to mammals, whereas group A genes are used for species-specific bitter tastants. The analysis also indicated that phylogenetically closely-related T2R genes are close in their chromosomal locations, supporting tandem gene duplication as the primary source of the production of new T2Rs. For those closely related paralogous genes, a significantly higher rate of nonsynonymous nucleotide substitution than that of synonymous substitution was observed in the extracellular regions of T2Rs, which are presumably involved in tastants binding. This suggests the role of positive selection in the diversification of newly duplicated T2R genes. Because many natural poisonous substances are bitter, so we conjecture that the mammalian T2R genes are under diversifying selection for the ability to recognize a diverse array of poisons that the organisms may encounter in exploring new habitats and diets. We not only investigated the evolutionary pathways of bitter receptor, but also those of sweet and umami receptors using bioinformatic and phylogenetic analyses. Our results revealed the distantly evolutionary relationship and different evolutionary pathways between bitter and sweet/ umami receptors, suggesting that different evolutionary pathways may result in the differences of these three receptors in function. The vomeronasal receptor 1 (V1R) are believed to be pheromone receptors in mammals. We used computational methods to identify 152 and 115 putative V1R genes from the draft rat and mouse genome sequence, respectively. The rat VIR repertoire consists of eleven subfamilies, ten of which are shared with the mouse; rat appears to lack the H and I subfamilies found in mouse and possesses one unique subfamily (M). Phylogenetic analysis of the V1R genes suggests that the birth-and-death process, characterized by frequent gene duplication and gene deactivation, dominates V1R evolution. All the sampled subfamilies originated after the divergence of rodents and primates, suggesting that V1R diversity in rodents reflects the dynamics of gene duplication and loss, genetic drift and natural selection within the rodent lineage. The analysis also revealed that most clusters within different subfamilies underwent an expansion very close to the split of mouse and rat. In addition, maximum likelihood analysis showed that the nonsynonymous and synonymous rate ratio for these clusters was much higher than one, suggesting the role for positive selection in the diversification of these duplicated V1R genes. Because V1R is thought to mediate the process of signal transduction in response to pheromone detection, so we speculate that the Y1R genes have evolved under the positive Darwinian selection to maintain the ability to discriminate between large and complex pheromonal mixtures. |
| 语种 | 中文 |
| 公开日期 | 2010-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6192]  |
| 专题 | 昆明动物研究所_分子进化基因组学 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 | 施鹏 . 哺乳动物适应性进化的分子机制探讨——若味受体基因和犁鼻器受体1基因的研究[D]. 北京. 中国科学院研究生院. 2004. |
入库方式： OAI收割
来源：昆明动物研究所
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