Prickett M D, Smarz T R, Adams J H
Department of Biological Sciences, University of Notre Dame, IN 46556.
Mol Biochem Parasitol. 1994 Jan;63(1):37-48. doi: 10.1016/0166-6851(94)90006-x.
The microneme protein-1 (MP-1) of Plasmodium knowlesi and Plasmodium vivax facilitates merozoite invasion of the erythrocyte by binding to Duffy blood group antigens. Since this protein is important in the invasion process and is a potential vaccine candidate, it is important to understand the nature of diversity within the MP-1 gene. Nine MP-1 gene sequences were compared from 2 isolates of P. knowlesi and a laboratory strain of P. vivax. The MP-1 genes of P. knowlesi were dimorphic based upon the central hydrophilic regions (III and IV) that were well conserved as alpha and beta types. Other regions were conserved among all P. knowlesi genes except for the amino cysteine-rich region (region II), a region predicted to be the initial contact site of the erythrocyte binding domain. Two distinct sequence motifs and part of a third were identified in region II that had a common identity of 68%. In some MP-1 genes recombination had occurred to create hybrids of the two sequence types. All cysteines and aromatic amino acids of region II were conserved in all genes or within a sequence type. There were 2 apparent recombination points within region II where switching occurred between sequence types. Another possible recombination site, identified as a common sequence motif, was identified in the middle of the hydrophilic region, at the beginning of regions III or IV. Nonsynonymous mutations within region II were biased towards radical amino acid changes, especially towards the carboxyl third, where there were 3 distinct types of sequence. Most synonymous and nonsynonymous nucleotide mutations within regions I, V, and VI were infrequent, individual events and not associated with any particular sequence type. Cysteine-rich regions of the P. vivax MP-1 gene compared to the P. knowlesi genes were characterized by an increased number of synonymous and nonsynonymous changes. This data identifies 2 mechanisms for generation of diversity in the MP-1 gene family, intergenic recombination and nucleotide mutations. Both may be mechanisms the parasite uses to evade the host immune response or to alter erythrocyte receptor specificity.
诺氏疟原虫和间日疟原虫的微小膜蛋白-1（MP-1）通过与达菲血型抗原结合促进裂殖子侵入红细胞。由于该蛋白在侵入过程中很重要且是潜在的疫苗候选物，因此了解MP-1基因内的多样性本质很重要。对来自2株诺氏疟原虫和1株间日疟原虫实验室菌株的9个MP-1基因序列进行了比较。诺氏疟原虫的MP-1基因基于中心亲水区（III和IV）呈二态性，这些区域作为α和β类型保存得很好。除富含氨基半胱氨酸的区域（区域II）外，所有诺氏疟原虫基因的其他区域均保守，该区域预计是红细胞结合域的初始接触位点。在区域II中鉴定出两个不同的序列基序和第三个基序的一部分，它们的共同一致性为68%。在一些MP-1基因中发生了重组，产生了两种序列类型的杂种。区域II的所有半胱氨酸和芳香族氨基酸在所有基因中或在一种序列类型内保守。区域II内有2个明显的重组点，序列类型之间发生了转换。在亲水区中部、区域III或IV开始处鉴定出另一个可能的重组位点，被确定为一个共同的序列基序。区域II内的非同义突变倾向于发生氨基酸的根本性变化，尤其是在羧基末端三分之一处，那里有3种不同类型的序列。区域I、V和VI内的大多数同义突变和非同义突变很少见，是个别事件，与任何特定的序列类型无关。与诺氏疟原虫基因相比，间日疟原虫MP-1基因的富含半胱氨酸区域的特征是同义变化和非同义变化的数量增加。该数据确定了MP-1基因家族中产生多样性的2种机制，基因间重组和核苷酸突变。两者都可能是寄生虫用于逃避宿主免疫反应或改变红细胞受体特异性的机制。
