SEXUAL COMPATABILITY AMONG P FALCIPARUM STRAINS

恶性疟原虫菌株之间的性相容性

• 批准号: 6170811
• 负责人: AKHIL B VAIDYA
• 金额: $ 31万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170811
• 关键词: Culicidae; Plasmodium falciparum; South America; alleles; genetic crossing over; genetic markers; genetic strain; geographic site; isolation /deprivation; linkage mapping; malaria; microorganism genetics; microorganism reproduction; nucleic acid probes; nucleic acid sequence; phenotype; sex behavior

The enormous number of Plasmodium falciparum infections in the world act to generate a vast reservoir of genetic variants, which can influence the pathogenesis, virulence, and drug sensitivity of these parasites. It is generally believed that P. Falciparum isolates are panmixic, i.e., mating randomly in the population. Recent work, however, indicates a pattern of nonrandom mating in some parts of the world. Furthermore, an investigation of maternally inherited cytoplasmic markers in a laboratory cross of well-characterized P. Falciparum clones HB3 and 3D7 revealed unidirectional mating in which the 3D7 clone dominated as the maternal parent. The prevalence of such mating behavior among various geographically distant P. Falciparum strains is unknown at present. Instances of unidirectional cytoplasmic incompatibility are known in many different species, and are often mediated by elements that cause genetic instability and hybrid dysgenesis in unidirectional manner. This often portends early stages of speciation. Hence, an understanding of mating compatibility among various P. Falciparum strains is important in the pursuit of knowledge regarding the emerging and reemerging global malaria situation. The hypothesis under which this project will operate states that P. Falciparum strains are undergoing nonrandom mating, and that unidirectional incompatibility affects parasite mating behavior. It is further hypothesized that a regulated genetic instability is an underlying factor that drives the incompatible mating behavior. Nonrandom mating could have a major impact on the spread of multi- locus traits such as the responses to immune surveillance and drug treatment within the parasite population. Three specific aims involving relatively straightforward approaches, but requiring labor intensive work, are proposed. In aim 1, cross-mating between well characterized P. Falciparum clones from Central America (HB3), Africa (3D7), Southeast Asia (W2), and South America (7G8) will be carried out, and the hybrid oocysts examined for their maternal lineage and directionality of the mating. In aim 2, independent recombinant progeny of the HB3 X 3D7 cross will be backcrossed to the HB3 parent to examine the possible nuclear locus that may dictate unidirectional mating. In aim 3, a genetic linkage map of the HB3 X 3D7 map will be derived using simple sequence length polymorphism markers. The map will aid in positional identification of the genes responsible for important biological properties of P. falciparum.

世界上大量的恶性疟原虫感染者 行为产生了巨大的遗传变异库，这可以影响 这些寄生虫的致病性、毒力和药物敏感性。 它 一般认为恶性疟原虫分离株是泛混的，即， 在种群中随机交配。 然而，最近的研究表明， 在世界某些地区非随机交配的模式。 此外，委员会认为， A母系遗传细胞质标记的研究 恶性疟原虫克隆HB 3和3D 7实验室杂交 揭示了单向交配，其中3D 7克隆占主导地位， 母亲 这种交配行为在各种动物中的流行程度 地理上遥远的恶性疟原虫菌株目前尚不清楚。 单向细胞质不亲和性的改变是已知的， 不同的物种，并往往介导的因素，导致遗传 不稳定性和杂种发育不全。 这往往 预示着物种形成的早期阶段 因此，对交配的理解 各种恶性疟原虫菌株之间的相容性在 追求知识的新兴和重新崛起的全球 疟疾情况。 这个项目运作的假设 指出恶性疟原虫菌株正在进行非随机交配， 单向不亲和性影响寄生虫的交配行为是 进一步假设，受调控的遗传不稳定性是一种 导致不相容交配行为的潜在因素。 非随机交配可能对多- 基因座特征，如对免疫监视和药物的反应 在寄生虫群体中进行治疗。 三个具体目标， 相对简单的方法，但需要劳动密集型 工作，建议。 在目标1中，充分表征的 P.来自中美洲（HB 3）、非洲（3D 7）、东南 亚洲（W2）和南美洲（7 G8）将进行，混合动力车 检查卵囊的母系谱系和卵囊的方向性， 交配 在目标2中，HB 3 X 3D 7的独立重组后代 杂交将与HB 3亲本回交，以检查可能的 核位点，可能决定单向交配。 在目标3中， 用简单序列分析法，将HB 3 × 3D 7连锁图进行作图 长度多态性标记 地图将有助于定位 确定负责重要生物学特性的基因 恶性疟原虫