Carlton Jane, Silva Joana, Hall Neil
The Institute for Genomic Research, Rockville, MD 20850, USA.
Curr Issues Mol Biol. 2005 Jan;7(1):23-37.
The field of comparative genomics of malaria parasites has recently come of age with the completion of the whole genome sequences of the human malaria parasite Plasmodium falciparum and a rodent malaria model, Plasmodium yoelii yoelii. With several other genome sequencing projects of different model and human malaria parasite species underway, comparing genomes from multiple species has necessitated the development of improved informatics tools and analyses. Results from initial comparative analyses reveal striking conservation of gene synteny between malaria species within conserved chromosome cores, in contrast to reduced homology within subtelomeric regions, in line with previous findings on a smaller scale. Genes that elicit a host immune response are frequently found to be species-specific, although a large variant multigene family is common to many rodent malaria species and Plasmodium vivax. Sequence alignment of syntenic regions from multiple species has revealed the similarity between species in coding regions to be high relative to non-coding regions, and phylogenetic footprinting studies promise to reveal conserved motifs in the latter. Comparison of non-synonymous substitution rates between orthologous genes is proving a powerful technique for identifying genes under selection pressure, and may be useful for vaccine design. This is a stimulating time for comparative genomics of model and human malaria parasites, which promises to produce useful results for the development of antimalarial drugs and vaccines.
随着人类疟原虫恶性疟原虫和啮齿动物疟疾模型约氏疟原虫全基因组序列的完成,疟原虫的比较基因组学领域最近已走向成熟。随着其他几个不同模型和人类疟原虫物种的基因组测序项目正在进行,比较多个物种的基因组需要开发改进的信息学工具和分析方法。初步比较分析的结果显示,在保守的染色体核心区域内,疟原虫物种之间的基因同线性具有显著的保守性,相比之下,亚端粒区域内的同源性降低,这与之前较小规模的研究结果一致。引发宿主免疫反应的基因通常是物种特异性的,尽管一个大型的变异多基因家族在许多啮齿动物疟原虫物种和间日疟原虫中很常见。来自多个物种的同线性区域的序列比对显示,物种之间编码区域的相似性相对于非编码区域较高,系统发育足迹研究有望揭示后者中的保守基序。比较直系同源基因之间的非同义替换率被证明是一种识别处于选择压力下的基因的强大技术,并且可能对疫苗设计有用。对于模型和人类疟原虫的比较基因组学来说,这是一个令人兴奋的时期,有望为抗疟药物和疫苗的开发产生有用的结果。