Microbial Genome Sequencing: Comparative Microbial Genome Analysis of the Human-Bacteroides Symbiosis

已向杰弗里一世博士提供赠款。作者声明：Richard K.位于圣路易斯的华盛顿大学的威尔逊博士对通常存在于人类肠道中的细菌的DNA进行测序。成年人是大量友好细菌的家园：总数超过了我们体内的人体细胞数量。最大的微生物集合存在于肠道中（10-100万亿个生物体）。这个由500-1000个物种组成的群落的基因组中嵌入的细菌基因的数量是我们人类基因组中基因数量的100倍。这些细菌基因的产物提供了在我们自己的基因组中没有完全进化的基本代谢能力，包括分解否则难以消化的营养物质的能力。 目前基因组学的革命提供了一个前所未有的机会，以确定正常肠道细菌群落的组成部分如何调节人类出生后发育和成年生理学的特征。 这项资助的重点是一组被称为拟杆菌的细菌，它们占人类肠道总微生物种群的约25%。拟杆菌属的几个成员的基因组将被测序，以确定它们如何成为肠道微生物群落的成功成员，并确定它们对人类生物学的贡献。另一组细菌的一个成员的基因组，真杆菌，进化上远离拟杆菌，但也在人类肠道中突出表现，将被测序，以确定成功的共生体的共同特征。促使这一分析的一个假设是，我们的细菌伙伴已经发展出合成新化学实体的能力，这些化学实体有助于建立和维持它们的互利关系，而对这些化学物质的探索，以及它们如何运作的特征，将为维持我们的健康和活力提供新的方法。在动态的、人口密集的生态系统如肠道中，细菌物种之间的基因交换可以对细菌进化和生理学产生重要影响（例如，抗生素抗性的传播）。因此，研究肠道细菌的基因组提供了一个机会，以解决有关环境如何影响物种的发展，它们在社区内灭绝的定义和意义，以及它们合作处理否则无法获得的营养物质的机制的一般性问题。研究共生体所采用的分子策略，以定义其环境中的稀缺性，在限制时管理对关键资源的访问，并决定分享商品以确保社会稳定，可能会产生对环境工程师，生态学家，经济学家，企业管理者以及那些研究，组织甚至管理我们人类社区的人重要的操作原则。

A grant has been awarded to Drs. Jeffrey I. Gordon and Richard K. Wilson of Washington University in St. Louis to sequence the DNA of bacteria that normally reside in the human intestine. The adult human is home to a vast number of friendly bacteria: the total number exceeds the number of human cells in our body. The largest collection of microbes resides in the intestine (10-100 trillion organisms). The number of bacterial genes embedded in the genomes of this community of 500-1000 species is ~100 times greater than the number of genes in our human genome. The products of these bacterial genes provide essential metabolic capacities not fully evolved in our own genome, including the ability to break down otherwise indigestible nutrients. The current revolution in genomics provides an unprecedented opportunity to define how components of the normal intestinal bacterial community modulate features of human postnatal development and adult physiology. This grant focuses on a group of bacteria known as Bacteroides that account for ~25% of the total microbial population in the human intestine. The genomes of several members of Bacteroides will be sequenced to determine how they have become such successful members of the gut microbial community and to define their contributions to human biology. The genome of a member of another group of bacteria, Eubacterium, evolutionarily distant from Bacteroides but also prominently represented in the human intestine, will be sequenced to identify features common to successful symbionts. One assumption prompting this analysis is that our bacterial partners have developed the capacity to synthesize novel chemical entities that help establish and sustain their mutually beneficial relationships, and that prospecting for these chemicals, and characterizing how they operate will suggest new ways to maintain our health and vigor. In a dynamic, densely populated ecosystem like the gut, exchange of genes between bacterial species can have important effects on bacterial evolution and physiology (e.g., propagation of antibiotic resistance). Therefore, studying the genomes of gut bacteria provides an opportunity to address general questions related to how environment affects development of species, the definition and meaning of their extinction within a community, and the mechanisms by which they cooperate to process otherwise inaccessible nutrients. Studying the molecular strategies employed by symbionts for defining scarcity in their environment, for managing access to crucial resources when they are limiting, and for making decisions about sharing goods to ensure societal stability may yield operating principles important to environmental engineers, ecologists, economists, business managers, and those who study, organize, and even govern our human communities.