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Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur in many Plasmodium falciparum isolates.

Sander AF, Salanti A, Lavstsen T, Nielsen MA, Magistrado P, Lusingu J, Ndam NT, Arnot DE - PLoS ONE (2009)

Bottom Line: This var gene is more conserved than other PfEMP1/var genes and is found in all P. falciparum isolates.One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates.Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype in pregnancy associated malaria.

View Article: PubMed Central - PubMed

Affiliation: Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, Faculty of Health Sciences, University of Copenhagen & Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

ABSTRACT

Background: The var2csa gene encodes a Plasmodium falciparum adhesion receptor which binds chondroitin sulfate A (CSA). This var gene is more conserved than other PfEMP1/var genes and is found in all P. falciparum isolates. In isolates 3D7, FCR3/It4 and HB3, var2csa is transcribed from a sub-telomeric position on the left arm of chromosome 12, but it is not known if this location is conserved in all parasites. Genome sequencing indicates that the var2csa gene is duplicated in HB3, but whether this is true in natural populations is uncertain.

Methodology/principal findings: To assess global variation in the VAR2CSA protein, sequence variation in the DBL2X region of var2csa genes in 54 P.falciparum samples was analyzed. Chromosome mapping of var2csa loci was carried out and a quantitative PCR assay was developed to estimate the number of var2csa genes in P.falciparum isolates from the placenta of pregnant women and from the peripheral circulation of other malaria patients. Sequence analysis, gene mapping and copy number quantitation in P.falciparum isolates indicate that there are at least two loci and that both var2csa-like genes can be transcribed. All VAR2CSA DBL2X domains fall into one of two distinct phylogenetic groups possessing one or the other variant of a large (approximately 26 amino acid) dimorphic motif, but whether either motif variant is linked to a specific locus is not known.

Conclusions/significance: Two or more related but distinct var2csa-type PfEMP1/var genes exist in many P. falciparum isolates. One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates. Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype in pregnancy associated malaria.

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Related in: MedlinePlus

Phylogenetic relationships between VAR2CSA DBL5ε sequences.A neighbor joining tree showing the relationships between 33 different VAR2CSA DBL5ε sequences, including eight sequences derived from samples which are known to have two or more var2csa-type genes/haploid genome. Sequences derived from the same genome are presented in the same color. Bootstrap values for each clade are shown at the nodes of the tree.
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pone-0006667-g007: Phylogenetic relationships between VAR2CSA DBL5ε sequences.A neighbor joining tree showing the relationships between 33 different VAR2CSA DBL5ε sequences, including eight sequences derived from samples which are known to have two or more var2csa-type genes/haploid genome. Sequences derived from the same genome are presented in the same color. Bootstrap values for each clade are shown at the nodes of the tree.

Mentions: The phylogenetic relationship between DBL5ε sequences derived from the same genome and an essentially random sample of other DBL5ε sequences is shown in Figure 7. The tree does not support the hypothesis that multiple var2csa–type genes are the result of recent duplication events in most isolates, although the HB3 and 1627 sequences are quite closely related and could represent relatively more recent duplications. In at least some of the genomes analyzed, the two genes appear to have been evolving independently for sufficient time to have diverged considerably.


Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur in many Plasmodium falciparum isolates.

Sander AF, Salanti A, Lavstsen T, Nielsen MA, Magistrado P, Lusingu J, Ndam NT, Arnot DE - PLoS ONE (2009)

Phylogenetic relationships between VAR2CSA DBL5ε sequences.A neighbor joining tree showing the relationships between 33 different VAR2CSA DBL5ε sequences, including eight sequences derived from samples which are known to have two or more var2csa-type genes/haploid genome. Sequences derived from the same genome are presented in the same color. Bootstrap values for each clade are shown at the nodes of the tree.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2723927&req=5

pone-0006667-g007: Phylogenetic relationships between VAR2CSA DBL5ε sequences.A neighbor joining tree showing the relationships between 33 different VAR2CSA DBL5ε sequences, including eight sequences derived from samples which are known to have two or more var2csa-type genes/haploid genome. Sequences derived from the same genome are presented in the same color. Bootstrap values for each clade are shown at the nodes of the tree.
Mentions: The phylogenetic relationship between DBL5ε sequences derived from the same genome and an essentially random sample of other DBL5ε sequences is shown in Figure 7. The tree does not support the hypothesis that multiple var2csa–type genes are the result of recent duplication events in most isolates, although the HB3 and 1627 sequences are quite closely related and could represent relatively more recent duplications. In at least some of the genomes analyzed, the two genes appear to have been evolving independently for sufficient time to have diverged considerably.

Bottom Line: This var gene is more conserved than other PfEMP1/var genes and is found in all P. falciparum isolates.One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates.Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype in pregnancy associated malaria.

View Article: PubMed Central - PubMed

Affiliation: Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, Faculty of Health Sciences, University of Copenhagen & Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

ABSTRACT

Background: The var2csa gene encodes a Plasmodium falciparum adhesion receptor which binds chondroitin sulfate A (CSA). This var gene is more conserved than other PfEMP1/var genes and is found in all P. falciparum isolates. In isolates 3D7, FCR3/It4 and HB3, var2csa is transcribed from a sub-telomeric position on the left arm of chromosome 12, but it is not known if this location is conserved in all parasites. Genome sequencing indicates that the var2csa gene is duplicated in HB3, but whether this is true in natural populations is uncertain.

Methodology/principal findings: To assess global variation in the VAR2CSA protein, sequence variation in the DBL2X region of var2csa genes in 54 P.falciparum samples was analyzed. Chromosome mapping of var2csa loci was carried out and a quantitative PCR assay was developed to estimate the number of var2csa genes in P.falciparum isolates from the placenta of pregnant women and from the peripheral circulation of other malaria patients. Sequence analysis, gene mapping and copy number quantitation in P.falciparum isolates indicate that there are at least two loci and that both var2csa-like genes can be transcribed. All VAR2CSA DBL2X domains fall into one of two distinct phylogenetic groups possessing one or the other variant of a large (approximately 26 amino acid) dimorphic motif, but whether either motif variant is linked to a specific locus is not known.

Conclusions/significance: Two or more related but distinct var2csa-type PfEMP1/var genes exist in many P. falciparum isolates. One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates. Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype in pregnancy associated malaria.

Show MeSH
Related in: MedlinePlus