Inferring the Roadmap of Bacterial Gene Transfer

描述(申请人提供)：横向基因转移对细菌基因组进化几乎无处不在的影响，引入了广泛的新遗传物质，可以促进适应；在病原体中尤其如此，基因组岛引入了代谢功能，允许采用致病的生活方式。虽然大量横向转移的基因在受体基因组中被识别，但关于潜在供体池的信息有限。由于横向基因转移是一种如此强大的变革力量，捐赠者分类群的性质--包括它们的系统发育关系和代谢能力--为理解现有谱系的进化以及洞察它们的进化潜力提供了背景。关键的是，有几个理论和经验上的论据可以解释为什么捐赠者分类群不是从所有细菌中随机选择的，而是可能与接受者更密切相关。这样，细菌分支可能会在基因转移的影响下形成，而不是简单地反映共同基因的共同祖先。我们建议为最近获得的主要细菌分支的基因库确定可能的供体分类群。首先，将使用人工基因组框架来开发一种稳健的方法，用于利用和组合参数方法进行外源基因检测。其次，我们将利用上面建立的人工基因组和参数指南，开发基因簇和基因组分割方法来识别外源基因。这些方法将识别彼此相似的非典型基因组。他们的想法是，具有相似特性的非典型基因可能来自同一来源。使用这些基因簇，我们将通过外推系统发育方法来推断数据库中没有同源基因的供体分类群，从而确定它们可能的祖先。供体分类群的分配将通过一种新的复制偏向模式分析来验证，这使得我们能够将外来基因的链偏向模式与其供体分支中基因组的签名相关联，这在系统发育上可能非常广泛。这一框架将使我们能够检验这样的假设，即基因转移更频繁地发生在关系更密切的谱系之间。

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.