褐家鼠的基因组变异及其对化学信号与配偶选择的影响

The brown rat is one of the best known and most common rats, originates from the plains of Asia, northern China and Mongolia, and spread to other parts of the world sometime in the Middle Ages. The rat has four morphologically and geographically differentiated subspecies or populations throughout China. It has been long domesticated to laboratory rats serving as experimental models for life science researches, and there thus has a wealth of biological knowledge, of which its odortypes closely correlated with genotype of male rats can signal genetic backgrounds for olfaction-mediated mate choice by female rats, and the full genome sequencing (FGS) of the rat is known. The proposed research plan is directed to the first direction designated in the general project instruction as “genomic variation under neo-environments and molecular mechanism underlying adaptation to neo-environment” by comparing genetic variation and mate choice among different subspecies and sibling species (R. nitidus) of the brown rat. We are going to integrate genomic，behavioral，chemical and neural approaches and focus our work on (1) genomic analysis on genetic differentiation with especial reference to the genes sensitive to the changes in chemosensory system and environments; (2) changes in olfaction-mediated mate choice behavior; (3) divergences in odortypes indicated by the composition of urine-borne volatiles and major urine protein (MUP). In a brief, we aim to provide a profound insight into mutant genes and its potential effects on local adaptation,chemical signals and assortative mate choice and lay the groundwork for future speciation genes search. As a result, 3 to 5 high influential papers are expected to be published, and 3-5 postgraduate students will be trained.

褐家鼠(Rattus norvegicus)起源于我国北方，在我国有4个地理亚种，存在遗传分化，其“气味型”传载了一定的“基因型”信息，并调节配偶选择。本项目的申请方向为“新环境下的基因组变异及适应新环境的分子机制”，拟通过室内和野外的结合，运用比较基因组学、行为学、化学等方法，研究褐家鼠不同亚种及近缘种的 (1) 基因组变异特点，尤其是对环境和化学通讯系统变化敏感的基因的分化；(2)嗅觉介导的配偶选择行为的变化特点; (3)尿液气味分子组成及尿液主蛋白（MUP）的组成所反映的“气味型”的遗传分化。阐明遗传分化与嗅觉介导的配偶选择关系，锁定影响气味代谢和配偶选择行为的候选基因，为今后筛选生物种形成基因奠定基础。预计发表SCI论文3－5篇，培养研究生3－5名。

通过对褐家鼠四个亚种8个地理群体共45个个体的全基因组重测序，我们发现不同地理群体的褐家鼠种群具有明显的谱系结构，呈现了遗传分化，褐家鼠有效种群大小远低于另一广泛分布的啮齿动物——小家鼠，并且褐家鼠基因组的连锁不平衡随物理距离增加消减地比小家鼠基因组慢；褐家鼠基因组积累了许多高频的轻微有害的突变，但拥有的严重有害的突变却比小家鼠少。此外，该研究发现褐家鼠有效种群大小随历史波动比较大，在2万年前经历过一次瓶颈，这一瓶颈严重影响了褐家鼠基因组等位基因频率的分布和连锁不平衡模式。此研究首次揭示了褐家鼠基因组的变异特点，为研究自然选择和遗传漂变对哺乳动物基因组的影响提供了新的证据。. 通过对代表性群体Hrbm和Djym进行Fst分析和功能注释，发现199个位于启动子区、UTR区、外显子区和转录终止位点区的差异性基因组区间，其中有7个区间位于犁鼻器受体，9个区间位于嗅觉受体。我们进一步对这两个已经出现了遗传分化的地理群体的室内饲养实验种群进行了配偶选择及气味成分的比较分析。通过比较化学成分，我们发现这两个群体雄鼠的尿液挥发性信息素成分和非挥发性的主要尿液蛋白(MUPs)雄性信息素呈现显著差异。通过双向选择行为学测试，我们发现这些尿液成分的群体间变异影响了雌鼠的配偶选择，Hrbm的雌鼠对其群体内的雄鼠表现出了嗅觉喜好。通过对信息素产生器官——肝脏的转录组分析，我们发现Djym群体MUP4、MUP5和雄激素受体AR的mRNA表达显著高于Hrbm群体，而Lcn2、Nfe2和Popdc2的表达却低于Hrbm群体，这提示这些肝脏差异表达的基因可能影响了信息素产生。这些代表性群体信息素产生相关基因和感知基因的分析为研究褐家鼠野外种群的分化特点与性选择的关系奠定了基础。.