Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY 10065, USA.
Curr Opin Microbiol. 2012 Aug;15(4):456-62. doi: 10.1016/j.mib.2012.03.003. Epub 2012 Apr 13.
Investigations into the genetic basis underlying antigenic variation in malaria parasites have primarily described transcriptional regulation of the large, multi-copy gene families that encode red cell surface antigens. In particular, extensive alterations to chromatin structure and subnuclear localization have been shown to play key roles in mutually exclusive expression, gene silencing and activation, and epigenetic memory. However the mechanisms responsible for the generation of sequence diversity within these gene families, a characteristic that is equally important for a parasite's ability to avoid the host's immune response, remains poorly understood in malaria. Recent work in model organisms suggests that the mechanisms controlling gene activation and silencing might also contribute to preferential recombination between antigen encoding genes, thus linking these two key processes.
对疟原虫抗原变异背后的遗传基础的研究主要描述了红细胞表面抗原编码的大型多拷贝基因家族的转录调控。特别是,染色质结构和亚核定位的广泛改变被证明在相互排斥的表达、基因沉默和激活以及表观遗传记忆中发挥关键作用。然而,对于这些基因家族内序列多样性的产生机制,这对于寄生虫逃避宿主免疫反应的能力同样重要,在疟疾中仍然知之甚少。模型生物的最新研究表明,控制基因激活和沉默的机制也可能有助于抗原编码基因之间的优先重组,从而将这两个关键过程联系起来。