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A global evolutionary analysis of eukaryotic duplication processes

真核复制过程的全球进化分析

基本信息

批准号：
7555610
负责人：
Xiang Gao
金额：
$ 5.94万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7555610
关键词：
Affect Age Age Distribution Animal Model Architecture Area Attention Bioinformatics Birth Birth Rate Blast Cell Caenorhabditis elegans Chromatin Structure Classification Code DNA Insertion Elements DNA Sequence Rearrangement DNA Transposable Elements Death Rate Demography Disease Drosophila melanogaster Eukaryota Event Evolution Exons Functional RNA Fungi Model Gene Duplication Gene Structure Genes Genetic Genome Genomics Goals Growth Hereditary Disease Human Human Genetics Indium Intercistronic Region Intergenic DNA Introns Invertebrates Investigation Lead Link Mammals Messenger RNA Methods Minor Molecular Evolution Mouse-ear Cress Mus Nucleic Acid Regulatory Sequences Open Reading Frames Organism Oryza sativa Plants Population Genetics Positioning Attribute Process Proteins Publishing RNA Splicing Regulator Genes Relative (related person)Saccharomyces cerevisiae Site Source Structure Surveys Techniques Variant Work base duplicate genes genome sequencing genome wide association study genome-wide insight novel paralogous gene physical process sample fixation

项目摘要

DESCRIPTION (provided by applicant): Gene duplication is considered as the primary source of creating novel materials for genome evolution. It is also associated with many diseases of human genetic disorders. However, previous studies on gene duplication have been biased toward the events that involve the duplication of entire protein-coding genes (e.g., divergence of paralogs). Since duplication break-points arise completely independently of gene boundaries, many small duplication segments may happen within genes, i.e., internal gene fragment duplication. In this proposal, we plan to carry out genome-wide analyses to decipher whether/how gene architectures (e.g., intron birth) are affected duplication events that took place within genes during the evolution process (specific aim 1). In addition, no published studies have investigated the evolutionary process and effects on intergenic DNA regions through population genetics approach. Therefore, we propose to extend our analyses to intergenic DNAs to study their duplication dynamics and fixation process (specific aim 2). Through the proposed global analysis on the duplication processes in internal gene and intergenic region, both of which are poorly understood before, we will provide an unprecedented and unbiased spectrum of genome duplications in eukaryotes. We will carry out the global evolutionary analysis on duplication processes in eukaryotic model organisms with available whole genome sequences. For each organism, we will study the evolutionary demography of internal gene duplications, effects of internal duplication on gene structure variations, and the determinants of the fixation process on duplication products. Through characterization of the duplicated intergenic regions, we propose to identify the sequence with low divergence rate compare to their linked duplication regions as the potential functional elements in intergenic regions. Bioinformatics techniques, population genetics approaches and molecular evolution methods will be applied to achieve above goals. The results will be critical to understand a broad array of unsolved issues in evolutionary genetics, including the extent to which: duplication causes genomic expansion vs. contraction, internal duplication creates immediate changes in structure and function of duplicated genes, and the relative conserved non-coding region under selection, in addition to understanding the mutational basis of genetic disorders caused by duplication,

描述（由申请人提供）：基因复制被认为是创造用于基因组进化的新材料的主要来源。它还与人类遗传性疾病的许多疾病有关。然而，先前关于基因复制的研究偏向于涉及整个蛋白质编码基因的复制的事件（例如，旁系同源物的分歧）。由于复制断点的出现完全独立于基因边界，许多小的复制片段可能发生在基因内，即，内部基因片段重复。在这项提案中，我们计划进行全基因组分析，以破译基因结构（例如，内含子出生）是在进化过程中发生在基因内的受影响的复制事件（具体目标1）。此外，还没有发表的研究通过群体遗传学的方法来研究基因间DNA区域的进化过程和影响。因此，我们建议将我们的分析扩展到基因间DNA，以研究它们的复制动力学和固定过程（具体目标2）。通过对内部基因和基因间区域的复制过程的全局分析，我们将提供一个前所未有的和公正的真核生物基因组复制谱。我们将利用现有的全基因组序列对真核模式生物的复制过程进行全局进化分析。对于每种生物，我们将研究内部基因复制的进化人口学，内部复制对基因结构变异的影响，以及复制产物固定过程的决定因素。通过对重复的基因间区的表征，我们建议将与其连锁重复区相比具有低趋异率的序列鉴定为基因间区中的潜在功能元件。生物信息学技术、群体遗传学方法和分子进化方法将用于实现上述目标。这些结果对于理解进化遗传学中一系列尚未解决的问题至关重要，包括在多大程度上：复制导致基因组扩张与收缩，内部复制导致复制基因的结构和功能立即发生变化，以及相对保守的非编码区选择，除了理解由复制引起的遗传疾病的突变基础之外，