H.PYLORI POPULATION GENETICS AND GENOME EVOLUTION

描述（由申请人提供）：幽门螺杆菌（Hp）是遗传多样性最高的细菌种属之一。 我们初步的DNA为基础的系统发育分析表明，在西班牙的Hp基因型与东亚的不同，而在利马的秘鲁人的Hp基因型大多是西班牙样的。为这一赠款期提议的研究有四个主要具体目标。 AIM 1.为了更好地了解Hp的遗传多样性和基因组进化。 我们将扩大目前的系统发育研究，从其他美洲人在拉丁美洲的Hp菌株，测试预测，大多数这样的Hp菌株也将在大多数位点的西班牙样。任何Hp人群被发现是丰富的等位基因不像那些西班牙将进一步检查。 来自欧洲、亚洲和非洲其他地区的Hp也将被研究（i）以更好地了解全球Hp人群的遗传结构，（ii）测试预测日本和西班牙的Hp基因库分别代表遗传多样性更高的东亚和欧洲基因库的子集。AIM 2.识别影响适应性的自然发生的等位基因差异并了解其基础。我们将测试我们发现的comB 9基因的东亚型等位基因在利马美洲印第安人的Hp中丰富的普遍性，并测试这是否反映了选择。更一般地说，将研究特定等位基因或基因异常丰度的其他情况，以鉴定在宿主相互作用特异性中重要的细菌性状。 将使用遗传操作的啮齿动物适应性Hp菌株以及小鼠和沙鼠感染模型来检查候选基因或等位基因对适合性的影响。AIM 3.为了研究家庭单位内的Hp进化动力学，将对秘鲁单个家庭中父母和子女的Hp菌株进行基因分型，以深入了解相关性，家庭内与社区传播，以及Hp在整体感染风险高的社会中的突变，重组和选择。AIM 4.检测社区之间的传播、混合感染和重组的可能性。 将对来自秘鲁日裔的Hp进行基因分型，以检测（i）祖先日本型基因的保留，与推定的秘鲁本土（西班牙型）菌株的社区获得;（ii）混合感染，特别是涉及不同种族来源的菌株，（iii）在短时间内重组的程度，以及（iv）特定基因或等位基因的选择。

DESCRIPTION (provided by applicant): Helicobacter pylori (Hp) are one of the most genetically diverse of bacterial species. Our preliminary DNA-based phylogenetic analyses showed that genotypes of Hp in Spain differ from those in East Asia, and that genotypes of Hp from Peruvians in Lima are mostly Spanish-like. The studies proposed for this grant period have four main specific aims. AIM 1. To better understand Hp genetic diversity and genome evolution. We will extend current phylogenetic studies to Hp strains from other Amerind people in Latin America, to test predictions that most such Hp strains will also be Spanish-like at most loci. Any Hp population found to be rich in alleles unlike those of Spain will be examined further. Hp from elsewhere in Europe, Asia and Africa will also be studied (i) to better understand Hp population genetic structure worldwide, (ii) test predictions that Hp gene pools in Japan and Spain represent subsets of more genetically diverse East Asian and European gene pools, respectively. AIM 2. To identify naturally occurring allele differences that affect fitness and understand their basis. We will test the generality of our finding that East Asian-type alleles of the comB9 gene are abundant in Hp from Amerinds in Lima, and test if this reflects selection. More generally, additional cases of unusual abundance of particular alleles or genes will be investigated to identify bacterial traits important in specificity of host interaction. Effects on fitness of candidate genes or alleles will be examined using genetically manipulated rodent-adapted Hp strains and mouse and gerbil infection models. AIM 3. To examine Hp evolutionary dynamics within family units, Hp strains from parents and children in individual Peruvian families will be genotyped to gain insights into relatedness, intrafamilial vs. community transmission, and mutation, recombination, and selection on Hp in societies where overall risks of infection are high. AIM 4. To detect transmission between communities, mixed infection, and potential for recombination. Hp from Japanese Peruvians will be genotyped to detect (i) retention of ancestral Japanese-type genes, vs. community acquisition of putative Native Peruvian (Spanish-type) strains; (ii) mixed infections, especially involving strains of different ethnic origins, (iii) extent of recombination in a brief time frame, and (iv) selection for particular genes or alleles.