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：
7408972
负责人：
Xiang Gao
金额：
$ 5.67万
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/7408972
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 Eukaryotic Cell Event Evolution Exons Functional RNA Fungi Model Gene Duplication Gene Structure Genes Genetic Genome Genomics Goals Growth Hereditary Disease Human 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 Rate Regulator Genes Relative (related person)Saccharomyces cerevisiae Site Source Standards of Weights and Measures Structure Surveys Techniques Variant Work base duplicate genes genome sequencing human disease insight novel paralogous gene physical process sample fixation size transposon/insertion element

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基因组进化新材料的主要来源。它还与人类遗传性疾病的许多疾病有关。然而，之前关于基因复制的研究偏向于涉及整个蛋白质编码基因复制的事件（例如旁系同源物的分歧）。由于重复断点的出现完全独立于基因边界，因此基因内可能发生许多小的重复片段，即内部基因片段重复。在本提案中，我们计划进行全基因组分析，以破译基因结构（例如内含子诞生）是否/如何受到进化过程中基因内发生的重复事件的影响（具体目标 1）。此外，还没有发表的研究通过群体遗传学方法研究进化过程以及对基因间DNA区域的影响。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态和固定过程（具体目标 2）。通过对内部基因和基因间区域的复制过程提出的全局分析（这两个过程以前人们对这两个过程知之甚少），我们将提供前所未有的、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型生物的复制过程进行全球进化分析。对于每种生物体，我们将研究内部基因重复的进化人口统计学、内部重复对基因结构变异的影响以及重复产物固定过程的决定因素。通过重复基因间区域的表征，我们建议将与其相连的重复区域相比具有低分歧率的序列识别为基因间区域中的潜在功能元件。将应用生物信息学技术、群体遗传学方法和分子进化方法来实现上述目标。这些结果对于理解进化遗传学中一系列未解决的问题至关重要，包括以下程度：重复导致基因组扩张与收缩，内部重复导致重复基因的结构和功能立即发生变化，以及相对保守的非基因组。选择下的编码区，除了了解重复引起的遗传性疾病的突变基础，