Molecular Evolution of Microbial Pathogen Genomes

微生物病原体基因组的分子进化

基本信息

批准号：
7372827
负责人：
NICOLE T PERNA
金额：
$ 30.71万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7372827
关键词：
Aerobic Animal Model Award Bacteria Bacterial Model Binding Sites Bioinformatics Biological Models Biological Process Case Study Communities Condition Cues Data Databases Elements Enterobacteriaceae Environment Escherichia coli Evolution Exercise Gene Transfer Genes Genetic Transcription Genome Genomics Growth Individual Infection Investigation Maps Mediating Metabolism Methods Molecular Molecular Evolution Numbers Operon Organism Orthologous Gene Other Resources Oxygen Pattern Personal Satisfaction Phylogenetic Analysis Play Prokaryotic Cells Rate Recording of previous events Regulation Regulon Research Role Signal Transduction Staging Structure System Testing Transcript Update Virulence Factors comparative experience genome sequencing improved insight microbial mutant novel pathogen pathogenic bacteria promoter research study response tool

项目摘要

DESCRIPTION (provided by applicant): With the explosive increase in genome sequencing, there appear to be an unprecedented number of bacteria under investigation at the molecular level; however, we need to exercise caution against over-interpretation of conserved genome contents. Vast sectors of our understanding of basic biological processes remain derived from a very small number of model organisms. Although orthologous genes can be identified with increasing reliability and ease, conserved function and conserved regulation are still assumptions, and little is known about the evolutionary dynamics underlying divergence of regulation in prokaryotes. In the previous period of this award, we successfully developed and applied multiple genome alignment tools to characterize the rates and patterns of genome evolution among enterobacteria and to delineate conserved and lineage-specific regions of genomes. Here, we continue dissecting the evolutionary history of this group of biomedically and agriculturally significant bacteria, extending our analyses to examine 1) the extent to which orthologous genes are regulated by orthologous regulators using orthologous binding sites, and 2) the integration of horizontally transferred genes into global regulons. The transcriptional response to growth in an oxygen- limited environment will serve as a case study of regulatory network evolution across the enterobacteria. We have selected this condition because it is well characterized in one model system, E. coli K-12, the transcriptional response involves a substantial number of genes, and metabolism in the presence or absence of oxygen plays a key role in defining environments permissible for bacterial growth such as pathogen survival in specific host environments. RELEVANCE: Pathogenic bacteria must regulate the expression of their genes during progressive stages of infection in response to a wide variety of external and internal environmental cues. Using genome sequence comparisons and experiments that dissect the response to varying concentrations of oxygen, an important factor in the host environment, we will determine the rates and patterns of regulatory system evolution across a group of biomedically and agriculturally significant bacteria. This will improve general models of bacterial regulatory evolution and provide specific insights into virulence factors regulated in an oxygen-dependent manner.

描述（由申请人提供）：随着基因组测序的爆炸性增长，在分子水平上研究的细菌数量似乎空前丰富；然而，我们需要谨慎对待保守基因组内容的过度解释。我们对基本生物过程的大部分理解仍然源自极少数的模式生物。尽管可以越来越可靠和容易地鉴定直系同源基因，但保守功能和保守调控仍然是假设，并且对原核生物调控分歧背后的进化动力学知之甚少。在该奖项的前一阶段，我们成功开发并应用了多种基因组比对工具来表征肠细菌基因组进化的速率和模式，并描绘基因组的保守和谱系特异性区域。在这里，我们继续剖析这组具有生物医学和农业意义的细菌的进化历史，扩展我们的分析以检查1）直系同源基因受直系同源调节子使用直系同源结合位点调节的程度，以及2）水平转移基因的整合进入全球调节子。对限氧环境中生长的转录反应将作为肠细菌调节网络进化的案例研究。我们选择这种条件是因为它在一个模型系统大肠杆菌 K-12 中得到了很好的表征，转录反应涉及大量基因，并且在有氧或无氧的情况下的新陈代谢在定义允许的环境中起着关键作用。细菌生长，例如病原体在特定宿主环境中的存活。相关性：致病细菌必须在感染的进展阶段调节其基因的表达，以响应各种外部和内部环境线索。通过基因组序列比较和实验来剖析对不同浓度氧气（宿主环境中的一个重要因素）的反应，我们将确定一组具有生物医学和农业意义的细菌的调节系统进化的速率和模式。这将改善细菌调节进化的一般模型，并为以氧依赖性方式调节的毒力因子提供具体的见解。