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DRAMATIC DIFFERENCE IN DIVERSITY BETWEEN PLASMODIUM FALCIPARUM AND PLASMODIUM VIVAX RETICULOCYTE BINDING-LIKE GENES

Malaria parasite proteins involved in erythrocyte invasion are considered important vaccine targets. Members of the reticulocyte binding-like (RBL) family of Plasmodium merozoite proteins are found in human, simian, and rodent malaria parasites and function in the initial steps of erythrocyte selection and invasion. The RBL genes are large, ranging in size from 7.7 to 10 kb, and the extent of any sequence diversity in parasite populations is unknown. We present the first assessment of sequence diversity within RBL genes from the two major human malaria parasites: Plasmodium falciparum and P. vivax. Polymorphism within the RBL genes is generally limited, except for P. vivax reticulocyte binding protein 2 (PvRBP2), which has nucleotide diversity levels 25-fold higher than the other RBL genes. The PvRBP2 haplotypes appear to fall into two distinct classes of alleles, suggesting large-scale dimorphism in this gene. Polymorphisms were frequently clustered, suggesting that different RBL domains may be evolving under different selection and functional pressures.

Received May 28, 2004. Accepted for publication November 29, 2004.

Financial support: Julian C. Rayner was supported by the Human Frontier Science Program and by the American Society of Microbiology as an American Society of Microbiology/National Center for Infectious Diseases Postdoctoral Research Fellow. This research was supported by grant number R01 AI24710-17 from the National Institutes of Health and by the National Center for Infectious Diseases, Centers for Disease Control and Prevention.

^* Both authors contributed equally to this work.

Authors’ addresses: Julian C. Rayner, Division of Geographic Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35209, Telephone: 205-934-5804, Fax: 205-934-5600, E-mail: jrayner{at}uab.edu. Tuan M. Tran and Mary R. Galinski, Emory Vaccine Center, Yerkes National Primate Research Center and Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30329, Telephone: 404-727-7214, Fax: 404-727-8199, E-mails: tmtran{at}emory.edu and galinski{at}rmy.emory.edu. Vladimir Corredor, Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia, E-mail: vcorred{at}rmy.emory.edu. Curtis S. Huber and John W. Barnwell, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, Telephone: 404-488-4528, E-mails: cwh7{at}cdc.gov and wzb3{at}cdc.gov.

Reprint requests: Mary R. Galinski, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329.

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