Ribacke Ulf, Mok Bobo W, Wirta Valtteri, Normark Johan, Lundeberg Joakim, Kironde Fred, Egwang Thomas G, Nilsson Peter, Wahlgren Mats
Swedish Institute for Infectious Disease Control, SE-17182 Solna, Sweden.
Mol Biochem Parasitol. 2007 Sep;155(1):33-44. doi: 10.1016/j.molbiopara.2007.05.005. Epub 2007 May 18.
The extent to which duplications and deletions occur in the Plasmodium falciparum genome, outside of the subtelomeres, and their contribution to the virulence of the malaria parasite is not known. Here we show the presence of multiple genome wide copy number polymorphisms (CNPs) covering 82 genes, the most extensive spanning a cumulative size of 110kilobases. CNPs were identified in both laboratory strains and fresh clinical isolates using a 70-mer oligonucleotide microarray in conjunction with fluorescent in situ hybridizations and real-time quantitative PCR. The CNPs were found on all chromosomes except on chromosomes 6 and 8 and involved a total of 50 genes with increased copy numbers and 32 genes with decreased copy numbers relative to the 3D7 parasite. The genes, amplified in up to six copies, encode molecules involved in cell cycle regulation, cell division, drug resistance, erythrocyte invasion, sexual differentiation and unknown functions. These together with previous findings, suggest that the malaria parasite employs gene duplications and deletions as general strategies to enhance its survival and spread. Further analysis of the impact of discovered genetic differences and the underlying mechanisms is likely to generate a better understanding of the biology and the virulence of the malaria parasite.
除端粒区域外，恶性疟原虫基因组中重复和缺失发生的程度及其对疟原虫毒力的影响尚不清楚。在此，我们展示了覆盖82个基因的多个全基因组拷贝数多态性（CNP）的存在，其中跨度最大的累计大小为110千碱基。使用70聚体寡核苷酸微阵列结合荧光原位杂交和实时定量PCR，在实验室菌株和新鲜临床分离株中均鉴定出了CNP。除6号和8号染色体外，在所有染色体上均发现了CNP，相对于3D7寄生虫，总共涉及50个拷贝数增加的基因和32个拷贝数减少的基因。这些基因最多可扩增至六个拷贝，编码参与细胞周期调控、细胞分裂、耐药性、红细胞入侵、性别分化及功能未知的分子。这些发现与之前的研究结果共同表明，疟原虫采用基因重复和缺失作为增强其生存和传播能力的通用策略。进一步分析所发现的遗传差异的影响及其潜在机制，可能会使我们对疟原虫的生物学特性和毒力有更深入的了解。
