Computing Regulatory DNA by Comparing Genomes

Pi：Michael Freeling(加州大学伯克利分校)这个为期两年的项目利用之前的工作，使用计算工具，以及已公布的序列和关于mRNA水平的数据，来假设高等植物中非编码序列的特定功能。该项目利用了最近发布的两个重要的古多倍体基因组--玉米和白菜。经过大约1200万年前的分化，这些古老的多倍体中的每一个都有可以作为外类群的近亲基因组-高粱和其他用于玉米和拟南芥的草，以及几个最近测序的卷心菜十字花科植物。有四个目标，目的是更好地了解增强子和顺式作用模块的功能，这些序列调控植物中的基因表达：1)开发COGE的新应用，在比较染色体片段的序列时，将基序和转录因子结合位点纳入视野。COGE是一个流行的公共工具箱，用于可视化和比较序列；2)通过发现与新的表达模式相对应的新序列的罕见情况，发现具有新调控能力的基因。寻找改变基因组显性模式的基因应该与这一目标有关；3)找到植物调控DNA进化到不可检测而又不失去其功能的方法，这一过程在哺乳动物中被称为“结合位点转换”；以及4)通过仅使用计算数据来利用分馏突变的自然过程来阐明植物中的增强子评估，以产生具有特定功能的特定序列。基于预测的增强子的假设将通过工程记者基因的瞬时和稳定表达来测试。该项目的广泛目标包括为服务不足的当地高中生提供暑期实习计划，以及继续开发广受欢迎的COGE网站(http://genomevolution.org/CoGe/))，该网站包含在比较基因和基因组时帮助找到意义的应用程序。这个项目每年暑假将接待一到两名学生。此外，该项目还包括改进目前由iPLANT(http://www.iplantcollaborative.org/))支持的COGE免费即时应用程序套件，这将为更广泛的科学界提供广泛的访问途径。

PI: Michael Freeling (University of California - Berkeley)This two year project leverages previous work and uses computational tools, along with published sequence and data on levels of mRNA, to hypothesize specific function for noncoding sequences in higher plants. The project takes advantage of the recent release of two important paleopolyploid genomes, maize and Brassica rapa (Chinese cabbage). Having diverged approximately 12 million years ago, each of these ancient polyploids has close relative genomes that can serve as outgroups - sorghum and the other grasses for maize and Arabidopsis, and several recently sequenced crucifers for the cabbages. There are four objectives with the goal of developing a better understanding of the function of enhancers and cis-acting modules, those sequences that regulate gene expression in plants: 1) to develop a new application for CoGe that brings motifs and transcription factor binding sites into view when comparing the sequences of chromosomal segments. CoGe is a popular, public toolbox for visualizing and comparing sequences; 2) to discover genes with new regulatory capabilities by finding rare cases of new sequence corresponding to new patterns of expression. Finding genes that switch their patterns of genome dominance should relate to this aim; 3) to find the means by which plant regulatory DNA evolves into non-detectability without losing its function, a process known as "binding site turnover" in mammals; and, 4) to elucidate enhancer evaluation in plants by using the natural process of fractionation mutagenesis to generate specific sequences with specific functions using computational data only. Hypotheses based on the predicted enhancers will be tested using transient and stable expression of engineered reporter genes.Broader aims of the project include a summer internship program for underserved, local high school students, and continued development of the popular CoGe website (http://genomevolution.org/CoGe/) containing applications that help find meaning when genes and genomes are compared. This project will host one or two students each summer. Additionally, this project involves improvements to the CoGe suite of free, on-the fly applications now powered by iPlant (http://www.iplantcollaborative.org/) that will provide broad access to the broader scientific community.