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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Antigens, Protozoan / genetics*
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Base Sequence
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Evolution, Molecular*
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Molecular Sequence Data
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Plasmodium / genetics
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Plasmodium / immunology
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Plasmodium falciparum / genetics*
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Plasmodium falciparum / immunology
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Protozoan Proteins / chemistry
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Protozoan Proteins / genetics*
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Sequence Alignment
Substances
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Antigens, Protozoan
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Membrane Proteins
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Protozoan Proteins
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merozoite surface protein 6, Plasmodium
Associated data
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GENBANK/EU305690
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GENBANK/EU305691
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GENBANK/EU305692
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GENBANK/EU305693
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GENBANK/EU305694
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GENBANK/EU305695
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GENBANK/EU305696
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GENBANK/EU305697
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GENBANK/EU305698
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GENBANK/EU305699
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GENBANK/EU305700
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GENBANK/EU305701
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GENBANK/EU878439
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GENBANK/EU878440
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GENBANK/EU878441
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