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Evolutionary Analysis of Bacterial Genomes: High-Throughput Computational Tools

细菌基因组的进化分析：高通量计算工具

基本信息

批准号：
8323964
负责人：
LUAY NAKHLEH
金额：
$ 24.46万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-15 至 2014-08-14
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Like all forms of life, bacteria undergo evolution. However, unlike many other organisms, bacterial evolution is not one of strict vertical descent. Horizontal (or lateral) gene transfer (HGT), a process by which genetic material is transferred among distantly related species, is ubiquitous in the prokaryotic branch of the Tree of Life. In the presence of HGT, the evolutionary history of a set of organisms is not treelike; rather, it is reticulate. HGT plays a major role in microbial genome diversification, and is claimed to be rampant among various groups of genes in bacteria. Further, it is a major mechanism by which bacteria develop resistance to antibiotics. Two major challenges that face studies of bacterial genomes involve estimating the extent of horizontally transferred genes in them, and reconstructing their evolutionary history. The former bears great significance on understanding the evolutionary role HGT plays and making predictions about its occurrence, and the latter amounts to detecting the donors and recipients of horizontally transferred genes, helping to understand how bacteria acquire antibiotic resistance and how to develop more effective ones. Attempts at addressing the first challenge have led to conflicting results, whereas attempts at the second challenge have been limited. Estimates as to the extent of HGT in bacteria range from one extreme (HGT is so rampant, rendering a bacterial phylogenetic tree useless) to another (HGT is mere background noise overridden by the lineal descent signal). As for the challenge of reconstructing reticulate evolutionary histories, the progress is even less satisfactory, mainly due to the lack of accurate and efficient methods for reconstructing phylogenetic networks. Our objective is to develop computational tools for high-throughput genome-wide evolutionary analysis of bacterial genomes, with focus on the detection and reconstruction of HGT. To achieve this objective, we will develop: (1) Protocols for micro-level analyses of bacterial genomes, to estimate HGT rates. (2) A stochastic framework that combined population genetics and phylogenetics theories for medium-level analyses. (3) Algorithmic techniques for phylogenetic (macro-level) analyses of genomes for detecting HGT. (4) Software tools that implement the protocols and methodologies and make them available to the research community.

描述（由申请人提供）：与所有生命形式一样，细菌也在经历进化。然而，与许多其他生物体不同，细菌的进化并不是严格的垂直进化。水平（或横向）基因转移（HGT）是遗传物质在远缘物种之间转移的过程，在生命之树的原核分支中普遍存在。在 HGT 存在的情况下，一组生物体的进化历史不是树状的；相反，它是网状的。 HGT 在微生物基因组多样化中发挥着重要作用，据称在细菌的各个基因组中普遍存在。此外，它是细菌产生抗生素耐药性的主要机制。细菌基因组研究面临的两个主要挑战包括估计细菌中水平转移基因的范围以及重建其进化历史。前者对于了解HGT的进化作用并预测其发生具有重要意义，后者则相当于检测水平转移基因的供体和受体，有助于了解细菌如何获得抗生素耐药性以及如何开发更有效的抗生素耐药性。解决第一个挑战的尝试导致了相互矛盾的结果，而解决第二个挑战的尝试却受到限制。对细菌中 HGT 程度的估计范围从一个极端（HGT 如此猖獗，使得细菌系统发育树毫无用处）到另一种极端（HGT 只是被直系血统信号覆盖的背景噪音）。至于重建网状进化史的挑战，进展则更不令人满意，这主要是由于缺乏准确有效的重建系统发育网络的方法。我们的目标是开发用于细菌基因组高通量全基因组进化分析的计算工具，重点是 HGT 的检测和重建。为了实现这一目标，我们将开发： (1) 细菌基因组微观分析方案，以估计 HGT 率。 (2) 结合群体遗传学和系统发育理论进行中期分析的随机框架。 (3) 用于检测 HGT 的基因组系统发生（宏观水平）分析的算法技术。 (4) 实施协议和方法并将其提供给研究界的软件工具。