Trace the flow of genes in the gut microbiome of obese and lean twin pairs

人类肠道微生物群落是已知的最复杂和最多样化的群落之一，但其贡献 这些社区对人类健康构成的差异在很大程度上仍未得到探索。文化-- 独立的16S rRNA调查显示，健康人群的微生物群落存在很大差异。 成年人。然而，强大的选择压力和肠道内异质DNA的涌入提供了一种 横向基因转移的机会是无与伦比的，所以16S rRNA可能不能告诉我们全部情况。因此， 了解肠道中基因流动的模式，并将16S rRNA基因序列与肠道中其他基因序列联系起来 基因组是至关重要的。在项目3中，我们开发了强大的新统计工具来关联微生物群落 根据它们所包含的物种、基因、转录本和代谢物，并使用这些工具来提供 首次定量估计宿主遗传学和肥胖对人类构成的影响 微生物群落。具体地说，我们将通过将人类肠道中的物种和基因与 从它们到其他哺乳动物的肠道群落，以及数百个群落样本 从海洋到土壤的不同物理环境。然后我们将使用物种的分布 以及与人类肠道相关的基因，以了解肠道的变异性和多样性 个体内部和个体之间的群落与在其他物种中观察到的模式有关， 环境。我们将检验以下两个假设。(1)人类的肠道存在系统差异 与宿主遗传学和肥胖症相关的社区。(2)肠道环境中的强烈选择压力 通过获得具有特定功能的基因，如碳水化合物，导致适应 新陈代谢，通过横向基因转移。我们将通过开发强大的新技术来检验这些假设 方法检测横向基因转移，并将这些方法与我们的关联工具UniFrac相结合 微生物群落。该项目将利用来自单合子和双合子的群落样本 项目1中的双胞胎和他们的母亲，以及B.thetaiotaomicron和M.smithii的泛基因组序列 从项目2中，确定遗传相关性和肥胖症对基因和 存在于个体成年人类的肠道群落中的物种。

Human gut microbial communities are among the most complex and diverse known, yet the contributionof differences in the composition of these communities to human health remains largely unexplored. Culture- independent 16S rRNA surveys have revealed large differences in the microbial communities amonghealthy adults. However, the strong selective pressure and influx of heterogeneous DNA in the gut provides an unparalleled opportunity for lateral gene transfer, so 16S rRNA may not tell us the whole story. Thus, understanding patterns of gene flow in the gut and relating 16S rRNA gene sequences to the rest of the genome is critical. In Project 3, we develop powerful new statistical tools for relating microbial communities in terms of the species, genes, transcripts, and metabolites they contain, and use these tools to provide the first quantitative estimates of the effects of host genetics and obesity to the composition of the human microbial community. Specifically, we will place species and genes in the human gut in context by relating them to the gut communities of a wide range of other mammals, and to community samples from hundreds of different physical environments ranging from oceans to soils. We will then use the distribution of species and genes related to those in the human gut to understand how the variability and diversity of gut communities within and between individuals relates to patterns observed in other species and environments. We will test the following two hypotheses. (1)There are systematic differences in human gut communities related to host genetics and to obesity. (2)The strong selective pressure in the gut environment results in adaptation through the acquisition of genes with specific functions, such as carbohydrate metabolism, through lateral gene transfer. We will examine these hypotheses by developing powerful new methods to detect lateral gene transfer, and by combining these methods with UniFrac,our tool for relating microbial communities. This project will utilize the community samples from monozygotic and dizygotic twins and their mothers from Project 1, and the pan-genome sequences of B. thetaiotaomicron and M. smithii from Project 2, to determine the relative contributions of genetic relatedness and obesity to the genes and species present in the gut communities ofindividual adult humans.