Comparative molecular evolution of animal and plant RNA-interference: Building a general model of how RNAi facilitates complexity

这项研究将有助于了解分子工作方式的微小变化如何在生物组织和与环境相互作用方面产生巨大变化。预计这项工作将对社会产生广泛的积极影响。首先，这个项目应该通过详细说明分子的变化如何产生复杂性来提高公众对进化理论的理解。第二，在计算、进化和分子生物学领域培养博士后和研究生，预计将有助于培养下一代能够利用多个学科解决真实的问题的科学家。第三，计算生物学远程学习计划的扩展有望帮助增加STEM学科中代表性不足的群体的参与。最后，了解分子如何产生复杂性可能会推动生物技术、合成生物学和纳米技术等领域的未来创新。了解复杂生命如何通过分子系统的变化产生是进化生物学的核心目标。RNA干扰（RNAi）是一种在复杂动植物进化中发挥重要作用的分子系统。然而，人们对构成RNAi系统的蛋白质和RNA机制的分子变化如何促进动物和植物复杂性的快速飞跃知之甚少。该项目的目的是确定RNAi机制中的分子变化如何改变动物和植物中RNAi系统的工作。该项目的方法利用编码RNAi系统蛋白质组分的动物和植物基因序列的进化分析来确定重要的进化变化，现代和祖先分子的实验分析来确定进化变化对RNAi如何工作的影响，以及结构分析来表征进化变化改变RNAi功能的机制。通过比较动物和植物中类似RNAi系统的进化，该项目有望确定RNAi如何进化以促进生物复杂性的一般原则。

This research will help understand how small changes in the ways molecules work can produce big changes in how living things are organized and interact with their environment. This work is expected to generate broad positive impacts on society. First, this project should improve public understanding of evolutionary theory by detailing how changes in molecules can produce complexity. Second, the training of postdoctoral and graduate students at the interface of computational, evolutionary and molecular biology is expected to help produce a next generation of scientists able to use multiple disciplines to solve real problems. Third, the expansion of distance-learning programs in computational biology is expected to help increase participation of underrepresented groups in STEM disciplines. Finally, understanding how molecules produce complexity is likely to drive future innovations in fields such as biotechnology, synthetic biology and nanotechnology.Understanding how complex life arises through changes in molecular systems is a central goal of evolutionary biology. RNA interference (RNAi) is a molecular system recognized as important in the evolution of complex animals and plants. However, little is known about how molecular changes in the protein and RNA machinery comprising the RNAi system facilitated these rapid leaps in animal and plant complexity. The objective of this project is to determine how molecular changes in RNAi machinery altered the working of RNAi system in animals and plants. This project's methodology utilizes evolutionary analysis of animal and plant gene sequences encoding the protein components of RNAi system to identify important evolutionary changes, experimental analysis of modern day and ancestral molecules to determine the effects of evolutionary changes on how RNAi works, and structural analysis to characterize the mechanisms by which evolutionary changes alter RNAi function. By comparing the evolution of similar RNAi systems in animals and plants, this project is expected to determine the general principles governing how RNAi evolved to contribute to organism complexity.