Elucidating the Evolution of Microbial Genes, Genomes and Communities

阐明微生物基因、基因组和群落的进化

• 批准号: 10438701
• 负责人: Howard Ochman
• 金额: $ 41.99万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438701
• 关键词: Address; Adopted; Area; Bacteria; Bacterial Genome; Bacteriophages; Biological; Classification; Communities; Etiology; Eukaryota; Evolution; Gene Exchanges; Genes; Genetic; Genome; Genomics; Goals; Health; Human; Human Microbiome; Infection; Knowledge; Life Style; Metagenomics; Methods; Modeling; Modification; Organism; Pattern; Population; Population Genetics; Process; Recording of previous events; Renaissance; Research; Role; Route; Source; Species Specificity; System; Testing; Tropism; Untranslated RNA; Variant; Viral; Virus; base; dietary; gene function; genetic information; gut microbiome; insight; invention; microbial; microbial community; microbiome; microbiome analysis; microorganism; programs; trait

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.

项目概要/摘要 基因组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知识中获得的。 易处理的遗传系统的数量。相比之下，目前对微生物组的关注已经转移 旨在了解生命形式的广泛多样性，这些生命形式只能从序列中得知，并且其 功能是通过与已知或表征的生物体的同源性推断的。主要目标之一 我们的研究计划是通过采用基因组、计算和方法来连接这两种方法 直接测试非模型的角色、功能和适应性的实验方法 在微生物组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 研究结果表明，肠道内容物不仅存在高度的宿主物种特异性 微生物组，但某些细菌谱系已经与数百万的宿主共同多样化 年。我们将调查这种共同多样化在人类群体中是如何进展的，并且 通过测试它们在环境中的适应性作用，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。 人类的饮食特征受到强烈选择。我们还将深入了解进化论 通过分析在中检测到的新解决的菌株水平变异来了解人类微生物组的历史 群体遗传学框架中的微生物组。第二个主题领域询问新基因如何 功能起源于细菌基因组。大多数新基因形成模型都是基于 复制和修改现有的遗传信息，而忽略了更根本的问题 关于全新的基因如何从头出现。而在真核生物中，非编码序列 似乎可以作为从头基因起源的模板，在细菌中，虽然是间接的，但很强， 有证据表明噬菌体可能是新基因的发明来源。拟议的研究将确定 通过测试功能相关性和有益效果来研究新基因的起源机制 由整合到细菌基因组中的新病毒序列赋予。第三主题领域提出 使用新的方法来解决有关病毒在微生物群落中的作用的几个问题 开发了源自​​以前仅通过宏基因组已知的病毒的实验系统 序列。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——所有问题都将作为推论，或者完全没有答案，如果只有基因组的话 序列可用。最后，我们计划定义病毒之间基因交换的限制 建立有意义的生物单位分类的一致性并了解 具有新病原学、分布和宿主向性的菌株的出现的可能性。