GIARDIA--A MODEL FOR ANCIENT EUKARYOTE GENOME FUNCTIONS

作为功能生物基因组分析的模型，贾迪亚提供了 关于真核细胞起源的独特观点。这项建议 属于互动研究项目补助金(IRPG)，该基金将 与R01“贾第鞭毛虫：古代真核生物模型”的强协同作用 基因组分析“(Mitchell Sogin Pi，计划开始日期1998年2月1日)， 其总体目标是获得准确的序列和图谱 其中至少95%的信息虽小，但在进化上 至关重要的基因组。我们对一个经过精心挑选的推论函数的测试 样本将极大地扩展和验证序列信息。这个 统一这些生物分析的主要目标是获得对 基因创新导致了重要的 在真核细胞中的功能具有以下特定目的：观点 贾第虫是“前线粒体”的说法受到了我们的发现的挑战。 三个线粒体样基因的表达、定位和 我们将在具体目标1中分析活动。在具体目标2中，我们 将深入了解真核细胞内膜系统的进化 通过对三种贾第鞭毛虫蛋白二硫键异构酶的分析 无论是亲核的还是真核的。因为基因的组织 在真核生物中，物质越来越复杂，在具体目标3中，我们 将分析一个非常高转录密度的模型区来阐明 贾迪亚可以用来有效利用其有限的 基因组大小。在具体目标4中，我们要求具备分析能力 选择新的基因是因为它们有能力扩展我们对 真核细胞隔室或贾第鞭毛虫的复杂性 发病机制。该项目将提供对 真核生物的基本细胞机制的进化，以及特定的 关于一种重要的环境传播传染病的信息 探员。它具有揭示生物创新的独特潜力 反映了原核生物/真核生物的分化。

As a model for functional-biological genome analyses, Giardia provides unique perspectives on the origins of eukaryotic cells. This proposal belongs to an Interactive Research Project Grant (IRPG), which will synergize strongly with an R01 "Giardia: A Model for Ancient Eukaryote Genome Analysis" (Mitchell Sogin PI, projected start date Feb. 1. 1998), whose overall goal is to obtain accurate sequence and mapping information for at least 95 percent of this small, but evolutionarily crucial genome. Our tests of inferred function of a carefully selected sample will greatly extend and validate the sequence information. The major goal unifying these biological analyses is to obtain insights into the genetic innovations that led to compartmentalization of important functions in eukaryotic cells with the following Specific Aims: The view that Giardia is "pre-mitochondrial" has been challenged by our finding of three mitochondrial-like genes whose expression, location and activities we will analyze in Specific Aim 1. In Specific Aim 2, we will gain insights into the evolution of eukaryotic endomembrane systems by analyses of three giardial protein disulfide isomerases that have both pro- and eukaryotic properties. Since the organization of genetic material is increasingly complex in eukaryotes, in Specific Aim 3, we will analyze a model region of very high transcript density to elucidate strategies that Giardia can use to efficiently exploit its limited genome size. In Specific Aim 4, we request the capability to analyze novel genes chosen for their power to extend our understanding of the complexity of eukaryotic cellular compartments or of giardial pathogenesis. This project will provide novel insights into the evolution of basic eukaryotic cellular mechanisms, as well as specific information on an important environmentally transmitted infectious agent. It has the unique potential to reveal biological innovations reflective of the prokaryotic/eukaryotic divergence.