title: Plasmodium falciparum: worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2).
abstract: We examined patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2) of Plasmodium falciparum, a major dimorphic malaria vaccine candidate antigen, by analyzing 448 msp-2 alleles from all continents. We describe several nucleotide replacements, insertion and deletion events, frameshift mutations, and proliferations of repeat units that generate the extraordinary diversity found in msp-2 alleles. We discuss the role of positive selection exerted by naturally acquired type- and variant-specific immunity in maintaining the observed levels of polymorphism and suggest that this is the most likely explanation for the significant excess of nonsynonymous nucleotide replacements found in dimorphic msp-2 domains. Hybrid sequences created by meiotic recombination between alleles of different dimorphic types were observed in few (3.1%) isolates, mostly from Africa. We found no evidence for an extremely ancient origin of allelic dimorphism at the msp-2 locus, predating P. falciparum speciation, in contrast with recent findings for other surface malarial antigens.
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo (SP), Brazil. muferrei@usp.br
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hartl
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016054:DNA, Protozoan / Q000737:chemistry; D019143:Evolution, Molecular; D014644:Genetic Variation; D017780:Malaria Vaccines / Q000235:genetics*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium