Department of Internal Medicine, Division of Infectious Diseases, Weill Medical College of Cornell University, New York, NY, 10065.
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, 10065; Kirk W. Deitsch 1300 York Avenue, Box 62, New York, NY 10065.
Microbiol Spectr. 2014 Dec;2(6). doi: 10.1128/microbiolspec.MDNA3-0022-2014.
The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. These parasites invade and replicate within the circulating red blood cells of infected individuals leading to numerous disease manifestations, including severe anemia, altered circulation, and tissue inflammation. Malaria parasites are also known for their ability to maintain a chronic infection through antigenic variation, the ability to systematically alter the antigens displayed on the surface of infected cells and thereby avoid clearance by the host's antibody response. The genome of P. falciparum includes several large, multicopy gene families that encode highly variable forms of the surface proteins that are the targets of host immunity. Alterations in expression of genes within these families are responsible for antigenic variation. This process requires the continuous generation of new antigenic variants within these gene families, and studies have shown that new variants arise through extensive recombination and gene conversion events between family members. Malaria parasites possess an unusual complement of DNA repair pathways, thus the study of recombination between variant antigen encoding genes provides a unique view into the evolution of mobile DNA in an organism distantly related to the more closely studied model eukaryotes.
人类疟疾中最严重的形式是由原生动物寄生虫疟原虫引起的。这些寄生虫在感染个体的循环红细胞内入侵和复制，导致多种疾病表现，包括严重贫血、循环改变和组织炎症。疟原虫还以其通过抗原变异维持慢性感染的能力而闻名，即能够系统地改变感染细胞表面显示的抗原，从而避免被宿主的抗体反应清除。疟原虫的基因组包括几个大型的、多拷贝的基因家族，这些基因家族编码表面蛋白的高度可变形式，这些表面蛋白是宿主免疫的靶点。这些家族内基因表达的改变导致了抗原变异。这个过程需要在这些基因家族内不断产生新的抗原变异体，研究表明，新的变异体是通过家族成员之间广泛的重组和基因转换事件产生的。疟原虫具有不寻常的 DNA 修复途径，因此研究变异抗原编码基因之间的重组为研究与更密切研究的模式真核生物关系较远的生物体中移动 DNA 的进化提供了独特的视角。
