Elucidating the Evolution of Microbial Genes, Genomes and Communities

项目摘要/摘要 基因组学方法以研究微生物的方式催化了一场复兴。 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 易驯化的遗传系统的数量。相比之下，目前对微生物的关注已经转移了重点。 朝着理解生命形式的广泛多样性的方向发展，这些生命形式只能从序列中获知，并且其 功能是通过与已知或特有的生物体的同源性来推断的。在主要目标中， 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 在微生物群中占主导地位的生物体。三个主题领域中的第一个来自我们的 研究发现，肠道内容物不仅具有高度的寄主物种特异性 微生物群，但某些细菌谱系已经与它们的宿主共同多样化，超过数百万 好几年了。我们将调查这种共同多样化在人类群体中是如何进展的，以及 通过测试它们在宿主中的适应作用来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 在人类中易受强烈选择的饮食特征。我们还将深入了解 通过分析检测到的新的可分辨的应变水平变化来研究人类微生物组的历史 种群遗传学框架中的微生物组。第二个主题领域询问新的基因和 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，忽视了更根本的问题 关于全新基因是如何从头产生的。而在真核生物中，非编码序列 似乎是从头开始基因起源的模板，在细菌中有很强的，虽然间接的， 有证据表明，噬菌体可能是新基因的创造性来源。拟议的研究将确定 通过测试功能相关性和有益效果来产生新基因的机制 通过整合到细菌基因组中的新病毒序列来实现。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，使用一种新的 开发的实验系统来自以前仅从元基因组中已知的病毒 序列。这个系统将允许我们解决与病毒宿主范围、生活方式和 相互作用-如果只有基因组，所有问题都将作为推论，或者完全没有答案 序列是可用的。最后，我们计划定义病毒之间的基因交换的限制 将它们统一归类为有意义的生物单位，并理解 有可能出现新的病原、分布和寄主取向的菌株。

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.