Inferring the Roadmap of Bacterial Gene Transfer

推断细菌基因转移的路线图

• 批准号: 7131452
• 负责人: Jeffrey G Lawrence
• 金额: $ 16.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7131452
• 关键词: Escherichia coli; bacterial genetics; computer simulation; functional /structural genomics; gene mutation; gene rearrangement; mathematical model; molecular dynamics; nucleic acid biosynthesis; nucleic acid quantitation /detection; nucleic acid sequence; operon

DESCRIPTION (provided by applicant): Lateral gene transfer is a nearly ubiquitous influence on bacterial genome evolution, introducing a wide palette of novel genetic material the can facilitate adaptation; this is especially true in pathogens, where genomic islands have introduced metabolic functions allowing the adoption of the pathogenic lifestyle. While a large number of laterally transferred genes are recognized in recipient genomes, information regarding potential donor pools is limited. Since lateral gene transfer is such a powerful force for change, the nature of donor taxa - including their phylogenetic relationships and metabolic capabilities - provides a context for understanding the evolution of extant lineages, as well as insight into their evolutionary potential. Critically, there are several theoretical and empirical arguments for why donor taxa may not be chosen at random from all bacteria, but rather may be more closely related to the recipients. In this way, bacterial clades may form under the influence of gene transfer, and may not simply reflect the common ancestry of shared genes. We propose to identify the likely donor taxa for the recently-acquired gene pools of major bacterial clades. First, an artificial genome framework will be used to develop a robust method for utilizing and combining parametric methods for alien gene detection. Second, we will develop both gene cluster and genome segmentation methods for the identification of alien genes, using artificial genomes and parametric guidelines established above. These methods will identify groups of atypical genes that are similar to one another. The idea is that atypical genes with similar properties may have originated from the same source. Using these clusters of genes, we will ascertain their likely ancestry by extrapolating phylogenetic methods to infer the donor taxa for genes without homologues in the database. The assignment of donor taxa will be verified by a novel analysis of replication bias patterns, allowing us to correlate strand-bias patterns of alien genes with the signatures of the genomes in their donor's clades, which can be phylogenetically quite broad. This framework will allow us to test the hypothesis that gene transfer occurs more often between more closely related lineages.

描述（由申请人提供）：横向基因转移对细菌基因组进化几乎是一种普遍存在的影响，引入了广泛的新遗传物质，可以促进适应;这在病原体中尤其如此，其中基因组岛引入了代谢功能，允许采用致病的生活方式。虽然大量的横向转移基因在受体基因组中被识别，但关于潜在供体库的信息是有限的。由于横向基因转移是如此强大的变化力量，供体类群的性质-包括它们的系统发育关系和代谢能力-为理解现存谱系的进化提供了背景，以及深入了解它们的进化潜力。关键的是，有几个理论和经验的论点，为什么供体类群可能不是随机选择从所有的细菌，而是可能更密切相关的受体。通过这种方式，细菌进化枝可能在基因转移的影响下形成，并且可能不仅仅反映共享基因的共同祖先。我们建议确定最近获得的主要细菌分支的基因库的可能的供体类群。首先，人工基因组框架将被用来开发一个强大的方法，利用和组合参数的方法来检测外来基因。其次，我们将开发基因簇和基因组分割方法，用于识别外来基因，使用人工基因组和上述参数指南。这些方法将识别彼此相似的非典型基因组。这个想法是，具有相似特性的非典型基因可能起源于同一来源。使用这些基因簇，我们将确定他们可能的祖先外推系统发育的方法来推断数据库中没有同源基因的供体类群。供体类群的分配将通过一种新的复制偏好模式分析来验证，这使我们能够将外来基因的链偏好模式与其供体分支中基因组的签名相关联，这可能是遗传学上相当广泛的。这一框架将使我们能够检验基因转移更经常发生在更密切相关的谱系之间的假设。