title: Sequence diversity and evolutionary dynamics of the dimorphic antigen merozoite surface protein-6 and other Msp genes of Plasmodium falciparum.
abstract: Immune evasion by Plasmodium falciparum is favored by extensive allelic diversity of surface antigens. Some of them, most notably the vaccine-candidate merozoite surface protein (MSP)-1, exhibit a poorly understood pattern of allelic dimorphism, in which all observed alleles group into two highly diverged allelic families with few or no inter-family recombinants. Here we describe contrasting levels and patterns of sequence diversity in genes encoding three MSP-1-associated surface antigens of P. falciparum, ranging from an ancient allelic dimorphism in the Msp-6 gene to a near lack of allelic divergence in Msp-9 to a more classical multi-allele polymorphism in Msp-7. Other members of the Msp-7 gene family exhibit very little polymorphism in non-repetitive regions. A comparison of P. falciparum Msp-6 sequences to an orthologous sequence from P. reichenowi provided evidence for distinct evolutionary histories of the 5' and 3' segments of the dimorphic region in PfMsp-6, consistent with one dimorphic lineage having arisen from recombination between now-extinct ancestral alleles. In addition, we uncovered two surprising patterns of evolution in repetitive sequence. First, in Msp-6, large deletions are associated with (nearly) identical sequence motifs at their borders. Second, a comparison of PfMsp-9 with the P. reichenowi ortholog indicated retention of a significant inter-unit diversity within an 18-base pair repeat within the coding region of P. falciparum, but homogenization in P. reichenowi.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, Bethesda, MD 20894, USA. royscott@ncbi.nlm.nih.gov
authors.forename: Scott W
authors.initials: SW
authors.lastname: Roy
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Weedall
authors.forename: Rogério L
authors.initials: RL
authors.lastname: da Silva
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Polley
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
mesh_terms: D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D001483:Base Sequence; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; C435213:merozoite surface protein 6, Plasmodium