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胃病原体幽门螺杆菌 (Hp) 在人类群体中如何进化，特别是遗传漂变和选择对细菌-宿主相互作用中重要基因的影响；最终，菌株的进化历史对其感染活力、毒力和人类疾病风险的影响。作为背景，幽门螺杆菌与消化性溃疡和胃癌有关，尽管大多数感染是良性的，有些甚至可能是有益的。 Hp 在遗传上极其多样化：独立分离株的保守管家基因 DNA 序列通常相差约 3%；不同的基因型组在不同的地区占主导地位（例如，西欧与东亚）。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”的菌株在大多数位点的序列上异常同质，但在两个粘附素基因上高度分歧；此外，这些 Shimaa 菌株的代表性基因与亚洲人相似，而来自城市秘鲁人（他们也主要是亚洲血统 >12,000 年前）的基因似乎大多是欧洲人的基因。我们假设 Shimaa 菌株遗传一致性反映了这个小型封闭群落中频繁的科间传播，以及对最适应菌株的有效选择；粘附素基因多样性反映了对宿主受体亲和力频繁变化的选择。在这里，我们建议 (i) 对两个或多个代表性 Shimaa 菌株的基因组进行测序； (ii) 在这些基因组中搜索其他已测序的 Hp 基因组中未出现的基因或等位基因类型（均来自欧洲人）； (iii) 使用根据 Shimaa 菌株基因组序列设计的微阵列通过比较杂交来寻找其他快速进化的基因。对来自诸如此类的特殊种群的菌株的比较研究可以非常有效，从而产生特殊的进化见解，通常适用于不同的致病、共生和有益微生物物种。