SEXUAL COMPATABILITY AMONG P FALCIPARUM STRAINS

世界上数量巨大的恶性疟原虫感染 产生大量的基因变异，这些变异可以影响 这些寄生虫的致病机制、毒力和药物敏感性。它 一般认为，恶性疟原虫分离株是全混合的，即， 在种群中随机交配。然而，最近的研究表明， 世界上某些地方的非随机交配模式。此外， 一种母系遗传的细胞质标记的研究 恶性疟原虫优良克隆株HB3和3D7的实验室杂交 揭示了以3D7克隆为主导的单向交配 母系父母。这种交配行为在不同物种中的流行率 目前尚不清楚地理距离较远的恶性疟原虫株系。 单向细胞质不亲和的例子在许多情况下都是已知的 不同的物种，并且通常是由导致基因 不稳定和杂交发育不全是单向的。这种情况经常发生 预示着物种形成的早期阶段。因此，对交配的理解 不同恶性疟原虫菌株之间的亲和性在 追求关于新兴和重新崛起的全球 疟疾情况。这个项目将在其下运行的假设 声称恶性疟原虫品系正在进行非随机交配，以及 这种单向不相容会影响寄生虫的交配行为。它是 进一步假设，受调控的遗传不稳定性是一种 驱动不相容交配行为的潜在因素。 非随机交配可能会对多发性交配的传播产生重大影响 基因座特征，如对免疫监测和药物的反应 在寄生虫种群中进行治疗。涉及的三个具体目标 相对简单的方法，但需要劳动密集型 工作，是提出的。在目标1中，很好地描述了 来自中美洲(HB3)、非洲(3D7)、东南部的恶性疟原虫克隆株 亚洲(W2)和南美(7G8)将进行，并混合 检查卵囊的母系血统和方向 交配。在目标2中，HB3X3D7的独立重组后代 杂交将回交到HB3亲本，以检查可能的 可能决定单向交配的核轨迹。在《目标3》中，一种基因 Hb3×3D7图谱的连锁图谱将用简单的序列得到 长度多态标记。这张地图将有助于定位 重要生物学特性相关基因的鉴定 恶性疟原虫。

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.