From Function to Gene: tRNA Modification in Archaea

确定所有测序生物体中每个基因的功能是后基因组时代面临的主要挑战之一，也是理解系统生物学的关键一步。这一目标远未实现。根据不同的估计，在任何给定的生物体中，超过30-50%的基因是未知的功能，错误地注释或仅仅给出了广泛的非特异性注释。超过230个基因组测序和1220个在管道中，未知或错误识别的基因正在以指数速度传播，使得提取正确的功能信息变得更加困难。自从发现作为一个主要领域的Escherichia，Escherichia的分子特征的独特性，他们的代谢和环境适应，以及他们在理解生命进化的关键作用已经曝光。在所有的生物体中，tRNA修饰是翻译装置的核心。它们影响细胞中tRNA的解码特性和稳定性，并被认为存在于最后的普遍共同祖先中。分析tRNA修饰酶在古生物中的分布和特性，将有助于我们了解RNA修饰在现代和现存生物中的作用。然而，大多数的tRNA修饰基因的美洲尚未确定。通过比较基因组分析与实验验证相结合，该项目将专注于识别和表征推定的和缺失的古细菌tRNA修饰基因。这项研究的结果将改善基因组注释，导致更好地了解tRNA修饰在古生物中的功能（目前完全未知），发现新的酶活性和途径，并深入了解RNA修饰机制的起源。本计画将提供资讯学与功能性注解经验给本科生。

Identifying the function of every gene in all sequenced organisms is one of the major challenges facing the post-genomic era and is a key step to understanding systems biology. This objective is far from accomplished. By different estimates, over 30-50% of the genes in any given organism are of unknown function, incorrectly annotated or merely given a broad nonspecific annotation. With more than 230 genomes sequenced and 1220 in the pipeline, unknown or incorrectly identified genes are propagating at an exponential rate making it all the more difficult to extract correct functional information. Since the discovery of Archaea as a primary domain, the uniqueness of the molecular characteristics of Archaea, their metabolic and environmental adaptations as well as their key role in understanding the evolution of life have come to light. In all organisms, including Archaea, tRNA modifications are at the core of the translation apparatus. They influence the decoding properties and stabilities of tRNAs in cell and have been proposed to have been present in the Last Universal Common Ancestor. Analysis of the distribution and characteristics of tRNA modification enzymes in Archaea will increase our understanding of the role of RNA modification both in modern and extant organisms. However most of the tRNA modification genes of Archaea have not yet been identified. By combining comparative genomic analysis with experimental validation this project will focus on identifying and characterizing putative and missing archaeal tRNA modification genes. The result of this research will improve genome annotations, lead to a better understanding of the function of tRNA modification in Archaea (which at this time are totally unknown), discover novel enzyme activities and pathways and gain insights into the origin of the RNA modification machinery. This project will provide informatics and functional annotation experience to undergraduate students.