Comparative Genomics of the Chlamydiaceae

我们打算将基因组学从对单个细菌基因组的表征扩展到对 传染病致病细菌的进化。衣原体，革兰氏阴性菌的一种细胞内专性 病原体是这种方法的理想选择。这一目的成员会引起一系列疾病，但仍在继续 难以进行传统的遗传分析。 我们的新的，多方面的方法，我们被称为“分类基因组学”，是首先对模式菌株进行测序 在以前或当前的项目中没有涉及的衣冠菌科物种-猪冠花、冠冠花和鹦鹉螺属(a 潜在的生物战剂)。此外，我们还将对考拉株的肺炎衣原体和大多数 衣原体的进化上遥远的成员，Waddlia chondroPhila和Simkania Negevens。要确定 那些可能被实验室适应的模式菌株丢失或被“野生”分离株获得的基因，我们 将通过汇集每个物种的多个分离物并减去那些共享的基因来应用消减杂交 按类型菌株分类。具有来自所有基因组代表的序列，以及来自 分类基因组差减，然后我们将从进化上创建一个所有已知ORF的基因数据库 与世隔绝的家庭。我们将利用这个数据库来设计一个非冗余的衣原体基因变异微阵列(称为 这里是“TaxoChip”)。在这项研究中，我们将使用TaxoChip进行一套比较基因组杂交(CGH) 使用我们从全球收集的一组独特的不同衣原体分离物进行实验。 我们希望利用这些基因组数据来研究衣原体的进化，并识别这些基因 这可能会区分观察到的宿主/组织生态位的多样性和导致的疾病结果。我们还将评估 水平基因转移在创造新的致病表型中的潜在重要作用以及可能的 动物和人类衣原体菌株之间的重要关系。此外，TaxoChip的设计和 衣原体基因数据库将对所有衣原体和分子进化学家都有长期的好处 越来越多地使用衣原体作为研究还原进化过程的标准模型。 这项研究的目的是解决广泛的问题，涉及遗传和进化的基础 衣原体的细胞内寄生和致病性的发展。在广泛的国际支持下 从科学界来看，我们认为这是一项开创性的建议，并预计它将成为一项基准研究 在比较微生物基因组学中。

We intend to extend genomics from the characterization of individual bacterial genomes to characterizing the evolution of infectious disease-causing bacteria. The Chlamydiales, an order of Gram-negative obligate intracellular pathogens, are ideally suited to this approach. Members of this order cause a range of diseases but continue to be refractory to conventional genetic analyses. Our novel, multifaceted approach, which we have named "Taxogenomics", is to first sequence the type strains of the Chlamydiaceae species not addressed by previous or current projects - C. suis, C. pecorum, and C. psittaci (a potential biological warfare agent). Additionally, we will sequence the koala strain of C. pneumoniae and the most evolutionarily distant members of the Chlamydiales, Waddlia chondrophila and Simkania negevensis. To identify those genes which may have been lost by the laboratory adapted type strains or been acquired by "wild" isolates, we will apply subtractive hybridization by pooling multiple isolates from each species and subtracting those genes shared by the type strain. With sequences from representatives of all genomes and with sequences derived from the taxonomic genomic subtractions, we will then create a gene database of all known ORFs from this evolutionarily isolated family. We will use this database to design a non-redundant microarray of Chlamydiales gene variation (called here the "Taxochip"). In this study, we will use the Taxochip in a suite of comparative genomic hybridization (CGH) experiments using a unique set of diverse Chlamydiales isolates that we have compiled from around the globe. We expect to use this genome data to investigate the evolution of the Chlamydiales and identify those genes that may differentiate the variety of observed host/tissue niches and resulting disease outcomes. We also will assess the potentially important role of horizontal gene transfer in creating novel pathogenicity phenotypes and the likely important relationship between animal and human chlamydial strains. Additionally, the Taxochip design and the Chlamydiales gene database will be of long-term benefit to all chlamydiologists and molecular evolutionists who are increasingly using the Chlamydiales as a standard model for studying reductive evolutionary processes. This study is designed to address broad questions that deal with the genetic and evolutionary basis of the development of intracellular parasitism and pathogenicity in the Chlamydiales. With broad and international support from the scientific community, we consider this a groundbreaking proposal and anticipate it will be a benchmark study in comparative microbial genomics.