Plasmodium falciparum: Worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2)

• Published in: Experimental parasitology 2007, Vol.115 (1), p.32-40
• Main Authors: Ferreira, Marcelo U., Hartl, Daniel L.
• Format: Article
• Language: English
• Subjects: Alleles; Allelic dimorphism; Amino Acid Sequence; Animals; Antigenic diversity; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; base pairs; Base Sequence; Biological and medical sciences; DNA, Protozoan - chemistry; Evolution; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genetic Variation; Life cycle. Host-agent relationship. Pathogenesis; Malaria; Malaria Vaccines - genetics; merozoite surface protein-1; merozoite surface protein-2; million years; Molecular Sequence Data; MSP-1; MSP-2; Myr; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Polymorphism, Genetic; Protozoa; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Recombination; Recombination, Genetic; repeat homology region; Repetitive Sequences, Nucleic Acid; RHR; Sequence Alignment; standard deviation; standard error of the mean; time to the most recent common ancestor; TMRCA; Vaccine development
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2006.05.003

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.