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

Exp Parasitol. 2007 Jan;115(1):32-40. doi: 10.1016/j.exppara.2006.05.003. Epub 2006 Jun 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / genetics*
  • Antigens, Protozoan / immunology
  • Base Sequence
  • DNA, Protozoan / chemistry
  • Evolution, Molecular*
  • Genetic Variation*
  • Malaria Vaccines / genetics*
  • Molecular Sequence Data
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / immunology
  • Polymorphism, Genetic
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / immunology
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Sequence Alignment

Substances

  • Antigens, Protozoan
  • DNA, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • merozoite surface protein 2, Plasmodium