Elucidating the Evolution of Microbial Genes, Genomes and Communities

项目总结/摘要 基因组学方法促进了微生物研究方式的复兴。 以前，大多数关于微生物过程和功能的知识都是从非常有限的 一些易处理的遗传系统。相反，目前对微生物组的关注已经转移了重点， 为了理解广泛多样的生命形式，这些生命形式只能从序列中得知， 通过与已知或特征化的生物体的同源性来推断功能。的主要目标之一， 我们的研究计划是通过采用基因组，计算和 直接测试非模型的角色、功能和适应性的实验方法 在微生物群落中占优势的微生物。三个主题领域中的第一个来自我们的 发现不仅在肠道内容物中存在高度的宿主种特异性， 微生物群落，但某些细菌谱系已经与其宿主共同多样化超过数百万， 年我们将研究这种共同多样化是如何在人类群体中发展的， 确定这些共同多样化的细菌是否以及如何与宿主相互作用， 在人类中受到强烈选择的饮食特征。我们还将深入了解 人类微生物组的历史，通过分析在 微生物组在群体遗传学框架。第二个主题领域询问新基因和 功能起源于细菌基因组。大多数新基因形成的模型都是基于 复制和修改现有的遗传信息，而忽略了更根本的问题， 全新的基因是如何从头产生的然而在真核生物中，非编码序列 似乎充当从头基因起源的模板，在细菌中，尽管是间接的， 噬菌体可能是新基因的创造性来源。这项研究将确定 通过测试新基因的功能相关性和有益效果， 由整合到细菌基因组中的新病毒序列赋予。第三个主题领域提出 为了解决有关病毒在微生物群落中的作用的几个问题，使用新的 开发的实验系统来源于以前仅从宏基因组学中已知的病毒 序列的该系统将使我们能够解决与病毒宿主范围、生活方式和 相互作用-所有的问题，将仍然作为推论，或完全没有答案，如果只有基因组 序列可用。最后，我们计划确定病毒之间基因交换的限制， 建立统一的分类到有意义的生物单位，并了解 具有新病原学、分布和宿主向性的菌株可能出现。

Project Summary / Abstract Genomic methods have catalyzed a renaissance in the way that microorganisms are being studied. Previously, most knowledge of microbial processes and functions was obtained from a very limited number of tractable genetic systems. In contrast, current focus on microbiomes has shifted emphasis towards understanding a broad diversity of lifeforms that are only known from sequences and whose functions are inferred by homology to known or characterized organisms. Among the primary goals of our research program is to bridge these two approaches by adopting genomic, computational and experimental methods that directly test the roles, functions and adaptations of the non-model organisms that predominate in microbiomes. The first of the three Subject Areas proceeds from our findings that not only is there a high degree of host species-specificity in the contents of gut microbiomes but certain bacterial lineages have been co-diversifying with their hosts over millions of years. We will investigate how this co-diversification has progressed within the human population, and determine if and how these co-diversifying bacteria interact with hosts by testing their adaptive role in a dietary trait that is subject to strong selection in humans. We will also gain insights into the evolutionary history of the human microbiome by analyzing the new resolved strain-level variation detected in microbiome in a population genetics framework. The second Subject Area asks how new genes and functions originate in bacterial genomes. Most models of new gene formation are based on the duplication and modification of existing genetic information, and ignore the more fundamental question about how completely new genes can arise de novo. Whereas in eukaryotes, non-coding sequences seem to serve as templates for de novo gene origination, in bacteria there is strong, though indirect, evidence that phage may be the inventive source of new genes. The proposed research will determine the mechanisms by which new genes originate by testing the functional relevance and beneficial effects conferred by new viral sequences integrated into bacterial genomes. The third Subject Area proposes to address several questions concerning the role of viruses in microbial communities using a newly developed experimental system derived from viruses known previously only from metagenomic sequences. This system will allow us to resolve issues relating to viral host ranges, lifestyles and interactions—all questions that would remain as inferences, or wholly unanswered, if only genome sequences are available. Finally, we our plan to define the limits of gene exchange among viruses both to establish uniformity in their classification into meaningful biological units and to understand the potential for strains with new etiologies, distributions, and host tropisms to emerge.