"Clonal" population structure of the malaria agent Plasmodium falciparum in high-infection regions
"Clonal" population structure of the malaria agent Plasmodium falciparum in high-infection regions
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DOI：
10.1073/pnas.0508871102
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发表时间：
2005-11-29
影响因子：
11.1
通讯作者：
Renaud, F
中科院分区：
文献类型：
--
作者：
Razakandrainibe, FG;Durand, P;Renaud, F
恶性疟疾病原体恶性疟原虫（Plasmodium falciparum）的种群遗传结构已被证明在低传染性地区主要是“无性繁殖”（即高度近亲繁殖）；在高传染性地区，它通常被认为是全身性的，或者几乎是全身性的，尽管很少有证据支持这一点。这个问题可以通过在蚊子载体的中肠卵囊中调查寄生虫的基因组成来解决，在那里可以直接观察到减数分裂的产物。恶性疟原虫的发育阶段为单倍体，但在受感染蚊子载体的卵囊中，两个配子融合，发生二倍体，随后发生减数分裂。我们通过分析来自肯尼亚11个地区的145只蚊子的613个卵囊，研究了位于5条染色体上的7个微卫星位点的遗传多态性。肯尼亚是恶性疟疾多发地区。有相当大的等位基因变异，16.3 +/- 2.1等位基因每个位点，和相当大的近交，接近50%的平均。近交是由自交（约占25%）和卵囊在蚊子肠道中的非随机基因型分布（35%）引起的。观察到杂合子的频率为0.43±0.03；假设随机配对，预期频率为0.80±0.05。在21个位点之间的两两比较中，连锁不平衡在统计学上是显著的，尽管有19个位点是在不同染色体上的位点之间进行的比较，这与panmixia的强烈偏差以及由此产生的基因组克隆繁殖一致，基因位点之间没有重组。这对于多位点药物和疫苗耐药性的传播具有相当大的进化意义和流行病学后果。
The population genetic structure of Plasmodium falciparum, the agent of malignant malaria, has been shown to be predominantly "clonal" (i.e., highly inbred) in regions of low infectivity; in high-infectivity regions, it is often thought to be panmictic, or nearly so, although there is little supporting evidence for this. The matter can be settled by investigating the parasite's genetic makeup in the midgut oocysts of the mosquito vector, where the products of meiosis can directly be observed. The developmental stages of A falciparum are haploid, except in the oocysts of infected mosquito vectors, where two gametes fuse, diploidy occurs, and meiosis ensues. We have investigated genetic polymorphisms at seven microsatellite loci located on five chromosomes by assaying 613 oocysts in 145 mosquitoes sampled from 11 localities of Kenya, where malignant malaria is perennial and intense. There is considerable allelic variation, 16.3 +/- 2.1 alleles per locus, and considerable inbreeding, approximate to 50% on the average. The inbreeding is caused by selfing (approximate to 25%) and nonrandom genotype distribution of oocysts among mosquito guts (35%). The observed frequency of heterozygotes is 0.43 +/- 0.03; the expected frequency, assuming random mating, is 0.80 +/- 0.05. Linkage disequilibrium is statistically significant for all 21 pairwise comparisons between loci, even though 19 comparisons are between loci in different chromosomes, which is consistent with strong deviation from panmixia and the consequent reproduction of genomes as clones, without recombination between gene loci. This is of considerable evolutionary significance and of epidemiological consequence, concerning the spread of multilocus drug and vaccine resistance.