Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
PLoS One. 2007 Jul 18;2(7):e613. doi: 10.1371/journal.pone.0000613.
The population genetics and structure of P. falciparum determine the rate at which malaria evolves in response to interventions such as drugs and vaccines. This has been the source of considerable recent controversy, but here we demonstrate the organism to be essentially sexual, in an area of moderately high transmission in the Lower Shire Valley, Malawi. Seven thousand mosquitoes were collected and dissected, and genetic data were obtained on 190 oocysts from 56 infected midguts. The oocysts were genotyped at three microsatellite loci and the MSP1 locus. Selfing rate was estimated as 50% and there was significant genotypic linkage disequilibrium (LD) in the pooled oocysts. A more appropriate analysis searching for genotypic LD in outcrossed oocysts and/or haplotypic LD in the selfed oocysts found no evidence for LD, indicating that the population was effectively sexual. Inbreeding estimates at MSP1 were higher than at the microsatellites, possibly indicative of immune action against MSP1, but the effect was confounded by the probable presence of null mutations. Mating appeared to occur at random in mosquitoes and evidence regarding whether malaria clones in the same host were related (presumably through simultaneous inoculation in the same mosquito bite) was ambiguous. This is the most detailed genetic analysis yet of P. falciparum sexual stages, and shows P. falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines.
疟原虫的种群遗传学和结构决定了疟疾在药物和疫苗等干预措施下的进化速度。这是最近相当大争议的来源，但在这里我们证明，在马拉维下谢里河谷的中度高传播地区，该生物基本上是有性的。收集并解剖了 7000 只蚊子，并从 56 只受感染的中肠获得了 190 个卵囊的遗传数据。卵囊在三个微卫星位点和 MSP1 基因座进行了基因分型。自交率估计为 50%，在 pooled oocysts 中存在显著的基因型连锁不平衡（LD）。更合适的分析方法是在异交卵囊和/或自交卵囊的单倍型 LD 中寻找基因型 LD，没有发现 LD 的证据，表明该种群实际上是有性的。在 MSP1 上的近交系数估计值高于微卫星，这可能表明对 MSP1 的免疫作用，但由于可能存在无效突变，这种效应受到了混淆。在蚊子中交配似乎是随机发生的，关于同一宿主中的疟疾克隆是否相关（大概是通过同一蚊子叮咬中的同时接种）的证据是模棱两可的。这是迄今为止对疟原虫有性阶段最详细的遗传分析，表明疟原虫是一种有性生物，其基因组处于连锁平衡状态，这有助于减缓耐药性和疫苗不敏感性的出现，延长药物和疫苗的可能有效治疗寿命。
