Comparative Genomics of the Chlamydiaceae

描述（由申请人提供）： 我们打算将基因组学从单个细菌基因组的表征扩展到表征引起传染病的细菌的进化。衣原体是革兰氏阴性专性细胞内病原体的一个目，非常适合这种方法。这一目的的成员引起一系列疾病，但仍然是传统的遗传分析难治。 我们的新的，多方面的方法，我们已经命名为“Taxogenomics”，是首先测序的模式菌株的衣原体物种没有解决以前或目前的项目- C。suis，C. pecorum和C.鹦鹉热（一种潜在的生物战剂）。此外，我们将测序考拉菌株的C。肺炎衣原体和衣原体目中进化上最远的成员，Waddlia chondrophila和Simkania negevensis。为了鉴定那些可能已经被实验室适应的典型菌株丢失或被“野生”分离株获得的基因，我们将通过汇集来自每个物种的多个分离株并减去那些由典型菌株共享的基因来应用消减杂交。利用来自所有基因组的代表序列和来自分类学基因组消减的序列，我们将创建来自这个进化上孤立的家族的所有已知ORF的基因数据库。我们将使用这个数据库来设计一个非冗余的衣原体基因变异的微阵列（这里称为“Taxochip”）。在这项研究中，我们将使用Taxochip在一套比较基因组杂交（CGH）实验，使用一套独特的不同的衣原体分离株，我们已经从地球仪汇编。 我们希望利用这些基因组数据来研究衣原体的进化，并确定那些可能区分各种观察到的宿主/组织生态位和由此产生的疾病结果的基因。我们还将评估水平基因转移在创造新的致病性表型中的潜在重要作用，以及动物和人类衣原体菌株之间可能的重要关系。此外，Taxochip的设计和衣原体基因数据库将长期受益于所有衣原体学家和分子进化论者谁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。 本研究的目的是解决广泛的问题，处理的遗传和进化的基础上发展的细胞内寄生和致病性的衣原体。在科学界的广泛和国际支持下，我们认为这是一个开创性的提议，并预计它将成为比较微生物基因组学的基准研究。

DESCRIPTION (provided by applicant): 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.