HELICOBACTER PYLORI GENOME SEQUENCE EVOLUTION

幽门螺杆菌基因组序列进化

• 批准号: 7936205
• 负责人: DOUGLAS Eugene BERG
• 金额: $ 11.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-26 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936205
• 关键词: Affinity; Alleles; American Type Culture Collection; Amerindian; Asians; Bacterial Adhesins; Benign; Clinical; Communicable Diseases; Communities; Comparative Study; DNA; DNA Sequence; Data; Databases; Deposition; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Drug Formulations; Epidemic; Europe; European; Evolution; Exploratory/Developmental Grant; Family; Far East; Gastric mucosa; Genes; Genetic Drift; Genome; Genomic Hybridizations; Genotype; Goals; Helicobacter pylori; Housekeeping Gene; Human; Individual; Infection; Modeling; Oligonucleotide Microarrays; Outcome; Peptic Ulcer; Peru; Population; Recording of previous events; Resources; Risk; Role; Stomach; Testing; Virulence; comparative; comparative genomics; density; design; genetic strain; genome sequencing; genome-wide; human disease; insight; interest; malignant stomach neoplasm; microbial; microbial disease; named group; novel; pathogen; programs; receptor; transmission process; tribal community

DESCRIPTION (provided by applicant): The overall goal of the exploratory R21 program studies proposed here is to better understand how the gastric pathogen Helicobacter pylori (Hp) evolves in human populations especially the impact of genetic drift and selection on genes important in bacterial-host interactions; and ultimately, the impact of a strain's evolutionary history on its vigor of infection, virulence and the risk of human disease. As background, Hp is implicated in peptic ulcer and gastric cancer, although most infections are benign, and some may even be beneficial. Hp is extremely diverse genetically: independent isolates typically differ by ~3% in DNA sequence of conserved housekeeping genes; and different sets of genotypes predominate in different regions (e.g., West Europe vs. East Asia). In preliminary studies we found strains from a remote Peruvian Amazon tribal community, the `Shima', to be unusually homogeneous in sequence at most loci, but highly divergent in two adhesin genes; in addition, representative genes from these Shimaa strains were Asian-like, whereas those from urban Peruvians (who are also of primarily Asian ancestry >12,000 yrs ago) seemed mostly European genetically. We hypothesize that Shimaa strain genetic uniformity reflects frequent inter-family transmission in this small closed community, and effective selection for best-adapted strains; and that adhesin gene diversity reflects selection for frequent change in host receptor affinities. Here we propose (i) to sequence the genomes of two or more representative Shimaa strains; (ii) to search these genomes for genes or allele types not represented in other already sequenced Hp genomes [each from ethnic Europeans]; and (iii) to find other rapidly evolving genes by comparative hybridization using microarrays designed from Shimaa strain genome sequences. Comparative studies of strains from special populations such as these can be immensely productive, leading to special evolutionary insights, generally applicable to diverse pathogenic, commensal and beneficial microbial species.

描述（由申请人提供）：此处提出的探索性R21计划研究的总体目标是更好地了解人群中胃病原体幽门螺杆菌（HP）如何在人群中演变，尤其是遗传漂移和选择对细菌宿主相互作用重要的基因的影响；最终，菌株的进化史对感染，毒力和人类疾病的风险的影响。作为背景，HP与消化性溃疡和胃癌有关，尽管大多数感染是良性的，甚至可能是有益的。 HP在遗传上非常多样化：独立的分离株在保守的管家基因的DNA序列中通常会差异约3％。不同地区（例如，西欧与东亚）的不同基因型占主导地位。在初步研究中，我们发现来自偏远的秘鲁亚马逊部落社区“ Shima”的菌株在大多数基因座的顺序上是异常均匀的，但在两个粘附基因中高度分歧。此外，来自这些Shimaa菌株的代表性基因类似于亚洲，而来自城市秘鲁人（也主要是亚洲血统> 12,000年）的基因似乎主要是欧洲遗传学的。我们假设Shimaa菌株遗传均匀性反映了这个小型封闭的社区中频繁的家庭间传播，并有效地选择了适应最适合的菌株。粘附素基因多样性反映了宿主受体亲和力频繁变化的选择。在这里，我们建议（i）对两个或多种代表性的Shimaa菌株的基因组进行测序； （ii）在其他已经测序的HP基因组中搜索这些基因组或未代表的基因或等位基因类型（每个来自欧洲族裔]； （iii）通过使用Shimaa菌株基因组序列设计的微阵列来查找其他快速发展的基因。从诸如此类的特殊人群中的菌株的比较研究可能具有巨大的生产力，导致特殊的进化见解，通常适用于多种致病性，共生和有益的微生物物种。