From Function to Gene: tRNA Modification in Archaea

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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.