Design of a bioinformatic database for functional evolutionary footprints in multigene families

了解新功能起源和现有基因功能多样化的分子基础在分子生物学中具有重要意义。基因复制可能是产生功能进化原料的主要机制，因为复制的副本可能通过在其编码序列中积累突变变化(替换)来获得新的功能。生化特性和这种变化在蛋白质序列中的位置是功能多样化的进化“足迹”。这些突变承受着强大的净化选择压力，以维持新的/修饰的功能。这个项目的目标是设计一个生物学数据库和一个信息系统，目标如下：1.设计和建立动物多基因家族中潜在功能上重要突变的数据库，以便于在以下情况下识别和探索进化足迹：(1)蛋白质序列背景[例如，α-螺旋]，(2)重复基因功能背景[例如，DNA结合活性]，以及(3)基因复制事件的系统发育背景[例如，脊椎动物-无脊椎动物的分化、哺乳动物的辐射]。开发一个通用的基于Web的客户/服务器资源，供世界各地的研究人员动态和交互地查询、检索、探索和分析进化足迹。拟议的进化足迹(EF)客户/服务器系统将对有兴趣探索进化足迹的研究人员有用，并将满足包括计算基因组学、进化生物学、免疫学、系统学和发育生物学在内的许多不同分子生物学领域的研究人员的日常需求。

Understanding the molecular basis for origin of new function and diversificaton of existing gene function is of fundamental importance in molecular biology. Gene duplications are possibly the predominant mechanism for generating raw materials for functional evolution, as the duplicate copies may acquire a new function by accumulating mutational changes (substitutions) in their coding sequences. Biochemical properties and the location of such changes in the protein sequence are the evolutionary "footprints" of functional diversification. These mutations are under strong purifying selection pressures to maintain the novel/modified function. The goal of this project is to design a biological database and an informatic system with the following objectives:1. Design and construction of a database of potentially functionally important mutations in animal multigene families to facilitate identification and exploration of the evolutionary footprints in the following contexts: (i) protein sequence context [e.g., alpha-helix], (ii) duplicate gene function context [e.g., DNA-binding activity], and (iii) phylogenetic context of gene duplication events [e.g., vertebrate-invertebrate divergence, radiation of mammals].2. Development of a general purpose Web-based client/server resource for researchers world-wide to dynamically and interactively query, retrieve, explore, and analyze evolutionary footprints.The proposed Evolutionary Footprint (EF) Client/Server System will be useful for researchers interested in exploring evolutionary footprints and will address the day-to-day needs of researchers in many different areas of molecular biology including computational genomics, evolutionary biology, immunology, systematics, and developmental biology.