人类与其他灵长类动物最主要的区别在于大脑的复杂性和与其相关的智力及生活习性等。人们在基因编码区、基因表达水平以及可选择性剪切等方面对大脑的适应性进化进行了大量的研究。可选择性poly(A)(APA)可以导致3’UTR长度的改变，是一种重要的mRNA异构体方式。基因组上超过70%的基因都具有APA位点，对基因的表达调控具有重要的作用。3'UTR长度的改变与神经信号传递、细胞增殖、免疫反应等多种生物学现象有关。我们前期的研究发现人类大脑偏好性的APA位点保守性更低，可能进化较快。在本项目中，我们将应用SAPAS技术，研究人类、黑猩猩、恒河猴、小鼠的大脑、肝脏及血液白细胞中的APA位点的使用情况，比较物种和组织APA位点的差异，鉴定进化较快的位点，分析这些位点自然选择压力；并研究这些APA位点改变的机制及生物学功能，从新的角度研究人类大脑的适应性进化。

The major characters of human different from other primates are cranial capacity and the derived complexity of brain, consciousness and life behavior. Many studies on the adaptive evolution were done based on the coding region, gene expression level,alternative splicing and so on. Alternative polyadenylation (APA) can lead to the changes of 3'UTR length, which increases the complexity of transcriptome. More than 70% of the human genes harbor APA sites, which plays an important role in gene regulation network. The changes of 3'UTR length are related to the neuron signal trasduction, cell proliferation, immune responses and other physiological process. Our previous studies have found that human brain-biased APA sites evolved faster than other sites. In this project, using our developed SAPAS technology, we will investigate the APA of human, chimpanzee, rhesus and mouse in several tissues (brain, liver and lymphocyte) in genome level. With this data, we will compare the species and tissue difference of APA, identify fast evolving sites and analyze the natural selection. We will also study the function of APA sites. In conclusion, we will study the adpative evolution of brain in a new angle of APA.