GENES NECESSARY FOR EXPRESSION OF A VIRULENCE DETERMINANT AND FOR TRANSMISSION OF PLASMODIUM-FALCIPARUM ARE LOCATED ON A 0.3-MEGABASE REGION OF CHROMOSOME-9
GENES NECESSARY FOR EXPRESSION OF A VIRULENCE DETERMINANT AND FOR TRANSMISSION OF PLASMODIUM-FALCIPARUM ARE LOCATED ON A 0.3-MEGABASE REGION OF CHROMOSOME-9
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DOI：
10.1073/pnas.90.17.8292
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发表时间：
1993-09-01
影响因子：
11.1
通讯作者：
KEMP, DJ
中科院分区：
文献类型：
--
作者：
DAY, KP;KARAMALIS, F;KEMP, DJ
布曼疟疾寄生虫恶性疟原虫的毒力被认为与被寄生的红细胞与毛细血管后微静脉内皮细胞的黏附(无性细胞黏附)有关。疟疾向蚊子媒介的传播涉及从无性发育到有性发育(配子细胞生成)的转变。恶性疟原虫体外连续培养常常导致无性细胞黏附和配子体发生不可逆转的丧失。利用脉冲场凝胶电泳法对表达不同表型的田间分离株和克隆系进行核型分析。这一分析表明，这两种表型的表达都定位于9号染色体的0.3-Mb亚端粒缺失。这种缺失经常发生在寄生虫分离株适应体外培养的过程中。带有此缺失的寄生虫不表达变异型表面凝集表型和可能的无性细胞黏附配基，命名为恶性疟原虫红细胞膜蛋白1，最近被证明经历了抗原性变异。无性细胞黏附和配子体发生之间的共线关系表明，这些表型的表达是遗传相关的。对这种联系的一种解释是，这两条发育途径都有共同的细胞黏附机制。这种提出的毒力因素(无性细胞黏附)和传播性(配子细胞生成)之间的生物和遗传联系将有助于解释为什么恶性疟原虫进化并保持了高度的毒力。
Virulence of the buman malaria parasite Plasmodium falciparum is believed to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual development (gametocytogenesis). Continuous in vitro culture of P. falciparum frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expression of these phenotypes were karyotyped by pulse-field gel electrophoresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion frequendy occurs during adaptation of parasite isolates to in vitro culture. Parasites with this deletion did not express the variant surface agglutination phenotype and the putative asexual cytoadherence ligand designated P. falciparum erythrocyte membrane protein 1, which has recently been shown to undergo antigenic variation. The syntenic relationship between asexual cytoadherence and gametocytogenesis suggests that expression of these phenotypes is genetically linked. One explanation for this linkage is that both developmental pathways share a common cytoadherence mechanism. This proposed biological and genetic linkage between a virulence factor (asexual cytoadherence) and transmissibffity (gametocytogenesis) would help explain why a high degree of virulence has evolved and been maintained in falciparum malaria.