Define conserved and variable elements of the pan-genomes of members of the adult

项目2是项目1中提出的一种补充方法，用于检查遗传 肥胖和消瘦双胞胎的微生物组多样性。而项目1研究基因组和 整个肠道微生物群落的代谢组学特性，项目2侧重于 肠道微生物群的两个重要成员，提供了微生物组的基因组锚定视图。的 发酵菌B。thetatiotaomicron和产甲烷古菌M.史密西已经在 gnotobiotic小鼠模型，对从饮食中获得能量具有协同效应。项目2探索 从瘦和肥胖单合子获得的这两种微生物物种的群体的基因组含量 双胞胎我们的中心假设是，肥胖个体的微生物组具有更大的能量能力 收获：因此，我们假设，可能有一个增强的能量获取功能，在 这两种微生物物种的基因组从肥胖个体获得。微生物基因组是一种 动态实体，由多种力量塑造，包括通过横向基因转移（LGT）的基因丢失和获得。 LGT的一个含义是没有单一的基因组序列可以描述一个“物种”。了解 一个微生物物种的性质，因此，我们必须关注“泛基因组”，核心的总和，垂直 遗传基因和可变的、菌株特异性基因。泛基因组的大小可能比基因组大得多 每一个分离株的DNA序列都在增加我们将确定 泛基因组，无论是在功能基因含量和新基因/分离物的发现率方面， 从MZ双胞胎及其母亲中分离的菌株，并根据其核心基因系统发育选择 （基于树的）关系在这个项目中，我们将使用包括培养 分离株，比较基因组杂交，基因组扩增和大规模DNA测序。使用 在项目1和3中概述的数据分析方法，我们将评估肥胖的功能后果- 在整个微生物肠道代谢方面的相关泛基因组差异，包括种间 协同作用此外，项目2中生成的数据将用作调查的起点 由Knightlaboratory在项目3中追踪肠道微生物组中的基因流。

Project 2 represents a complementary approach to the one presented in Project 1 for examining genetic diversity in the microbiomes of obese and lean twin pairs. Whereas Project 1 investigates genomic and metabolomic properties of the whole gut microbial community, Project 2focuses on the gene complement of two prominent members of the gut microbiota, offering a genome-anchored view of the microbiome. The fermentative bacterium B. thetatiotaomicron and the methanogenic archaeon M. smithii have been shown in gnotobiotic mouse models to have a synergistic effect on energy harvest from the diet. Project 2 explores the genomic content of populations of these two microbial species obtained from lean and obese monozygotic twins. Our central hypothesis is that the microbiome of obese individuals has a greater capacity for energy harvest: thus, we postulate that there may be an enhancement of energy-acquisition functions in the genomes of these two microbial species obtained from obese individuals. The microbial genome is a dynamic entity, shaped by multiple forces that include gene loss and gain via lateral gene transfer (LGT). One implication of LGT is that no single genome sequence can describe a 'species'. To understand the nature of a microbial species we therefore must focus on the "pan-genome", the sum of core, vertically inherited genes and the variable, strain-specific genes. Pan-genome size can be vastly larger than the genome of any single isolate, increasing with every isolate sequenced. Wewill determine the extent of variability in the pan-genomes, both in terms of functional gene content and the discovery rate of new genes/isolate, of strains isolated from MZ twin pairs and their mothers and selected based on their core gene phylogenetic (tree-based) relationships. In this Project, we will use a combination of methods including culturing of isolates, comparative genome hybridization, genome amplification and large-scale DNA sequencing. Using data analysis methods outlined in Projects 1 and 3, we will assess the functional consequences of obesity- related pan-genome differences in terms of overall microbial gut metabolism, including inter-species synergisms. In addition, the data generated in Project 2will be used as a starting point for the investigations by the Knightlaboratory in Project 3 to trace the flow of genes in the gut microbiome.