Identifying genetic code reassignments in nucleotide sequence databases

识别核苷酸序列数据库中的遗传密码重新分配

• 批准号: 9907623
• 负责人: Yekaterina Shulgina
• 金额: $ 3.22万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-16 至 2021-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907623
• 关键词: Accidents; Address; Amino Acid Sequence; Amino Acid Sequence Databases; Amino Acids; Base Sequence; Biological; Candida albicans; Charge; Codon Nucleotides; Communication; Computer Analysis; Computing Methodologies; DNA; DNA Sequence; Data; Data Set; Development; Ensure; Environment; Evolution; Freezing; Genbank; Genes; Genetic Code; Genetic Models; Genetic Variation; Genome; Homologous Protein; Human; Laboratories; Life; Mass Spectrum Analysis; Metagenomics; Methods; Mitochondria; Modernization; Mycoplasma pneumoniae; Nature; Northern Blotting; Oral; Organism; Peptide Sequence Determination; Process; Proteins; Proteome; Proteomics; Research Personnel; Research Training; Science; Tertiary Protein Structure; Testing; Training; Transfer RNA; Transfer RNA Aminoacylation; Translating; Translations; Trees; Update; Writing; Yeasts; career; comparative; computerized tools; contig; experimental study; follow-up; genetic predictors; genetic variant; genome annotation; in silico; laboratory equipment; molecular sequence database; novel; open source; pathogenic bacteria; pressure; programs; skills

Project Summary Abstract Biological discoveries made in other organisms tell us about the functions of human genes because of the ability to compare homologous protein sequences. Recent efforts to sequence a greater diversity of species for comparative analysis have been primarily done on the DNA level, and protein sequences are subsequently translated in silico assuming some genetic code. However, there is currently no informed way of selecting the correct genetic code for a newly sequenced organism, which is critical for the correct translation of predicted protein sequences. As more diverse organisms are sequenced, species using variant genetic codes continue to be found, suggesting that there may be a hidden diversity of alternative genetic codes across the tree of life. Aim 1 proposes building a computational tool to predict the genetic code used by an organism from nucleotide sequence alone. This would fill in a critical missing step in genome annotation pipelines and would ensure the accuracy of protein sequence databases, which are predominantly composed of predicted protein sequences. In aim 2, the computational tool will be used to infer the genetic code usage of all publicly available genomes and validate any new genetic codes by computational analysis of tRNA genes, experimental confirmation of tRNA expression via Northern blotting, and confirmation of altered codon translation via proteomic mass spectrometry. In aim 3, the updated distribution of alternative genetic codes will be used to address long-standing hypotheses in the field about how the genetic code is thought to evolve. This research training plan is intended to prepare the PI for a career as an independent and interdisciplinary researcher. The training environment will be in a collaborative computational laboratory, with access to a lab bench and shared lab equipment to do the proposed experiments. The training plan will also include development of science communication skills, including oral presentations and writing.

项目摘要 在其他生物体中的生物学发现告诉我们人类的功能 基因，因为能够比较同源蛋白质序列。最近努力 序列更大的物种多样性进行比较分析，主要是在 DNA水平和蛋白质序列随后在计算机上翻译，假设一些 遗传密码然而，目前还没有选择正确的遗传密码的知情方法 对于新测序的生物体，这对于预测蛋白质的正确翻译至关重要 序列的随着越来越多的生物体被测序，使用变异遗传密码的物种 继续被发现，这表明可能有一个隐藏的替代遗传多样性， 生命之树上的密码 目标1提出建立一个计算工具来预测遗传密码所使用的 单从核苷酸序列来看。这将填补基因组中关键的缺失步骤， 注释管道，并将确保蛋白质序列数据库的准确性， 主要由预测的蛋白质序列组成。在目标2中，计算工具将 用于推断所有公开可用的基因组的遗传密码使用，并验证任何新的 通过计算分析tRNA基因的遗传密码，实验证实tRNA 通过北方印迹表达，并通过蛋白质组学证实改变的密码子翻译 质谱分析法来在目标3中，将使用替代遗传密码的最新分布 解决该领域长期存在的关于遗传密码如何被认为是 进化 本研究培训计划旨在为PI作为独立研究员的职业生涯做好准备。 跨学科研究者。培训环境将是一个合作的环境。 计算实验室，可以使用实验台和共享实验室设备来完成 提出的实验。培训计划还将包括发展科学 沟通技巧，包括口头报告和写作。