Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis

BMC Genomics

Research Article

Christian Frech¹  Nansheng Chen¹ 

[1] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, B.C V5A 1S6, Burnaby, Canada;

关键词: Malaria parasites;    Plasmodium;    Comparative genomics;    Variant surface antigens;    Gene family classification;    Vaccine target;   

DOI  :  10.1186/1471-2164-14-427

 received in 2013-01-15, accepted in 2013-06-19,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPlasmodium parasites, the causative agents of malaria, express many variant antigens on cell surfaces. Variant surface antigens (VSAs) are typically organized into large subtelomeric gene families that play critical roles in virulence and immune evasion. Many important aspects of VSA function and evolution remain obscure, impeding our understanding of virulence mechanisms and vaccine development. To gain further insights into VSA function and evolution, we comparatively classified and examined known VSA gene families across seven Plasmodium species.ResultsWe identified a set of ultra-conserved orthologs within the largest Plasmodium gene family pir, which should be considered as high-priority targets for experimental functional characterization and vaccine development. Furthermore, we predict a lipid-binding domain in erythrocyte surface-expressed PYST-A proteins, suggesting a role of this second largest rodent parasite gene family in host cholesterol salvage. Additionally, it was found that PfMC-2TM proteins carry a novel and putative functional domain named MC-TYR, which is conserved in other P. falciparum gene families and rodent parasites. Finally, we present new conclusive evidence that the major Plasmodium VSAs PfEMP1, SICAvar, and SURFIN are evolutionarily linked through a modular and structurally conserved intracellular domain.ConclusionOur comparative analysis of Plasmodium VSA gene families revealed important functional and evolutionary insights, which can now serve as starting points for further experimental studies.

【 授权许可】

CC BY   
© Frech and Chen; licensee BioMed Central Ltd. 2013