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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

Chromosomal location of var2csa-type loci in P.falciparum isolates.Conditions for the separation of the chromosomes and DIG labeling and detection of the var2csa DBL3X domain-derived probe sequence are given in the Materials and Methods. Gel measuring rulers and superimposed alignment lines are shown. Marker chromosomes are from Hansenula wingei. Note that the two uppermost faint bands are not chromosomes but a PFG artifact. HB3, 3D7, FCR3/It4 and 7G8 are long term laboratory isolates whilst Tz745, Tz748, Tz752, Tz755, Tz788 and Tz796 are recent field isolates from Korogwe, Tanzania.
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pone-0006667-g005: Chromosomal location of var2csa-type loci in P.falciparum isolates.Conditions for the separation of the chromosomes and DIG labeling and detection of the var2csa DBL3X domain-derived probe sequence are given in the Materials and Methods. Gel measuring rulers and superimposed alignment lines are shown. Marker chromosomes are from Hansenula wingei. Note that the two uppermost faint bands are not chromosomes but a PFG artifact. HB3, 3D7, FCR3/It4 and 7G8 are long term laboratory isolates whilst Tz745, Tz748, Tz752, Tz755, Tz788 and Tz796 are recent field isolates from Korogwe, Tanzania.

Mentions: Figure 5 illustrates a separation of the 14 P.falciparum chromosomes and the corresponding Southern blot, probed with a DBL3X-derived var2csa-specific gene probe. To compensate for gel distortions each sample was run in duplicate. The PFG illustrates the chromosome length polymorphisms that are a feature of P.falciparum [49]. Confirming earlier experiments, chromosome 12 contains a var2csa gene locus, hybridized by the var2csa gene probe in all 10 isolates shown in Figure 5. Two of the isolates, HB3 and Tz748, have one additional locus hybridizing the var2csa probe, on chromosome 1 in HB3 and on what is probably chromosome 8 in Tz748 (hybridizing to the upper region of the poorly resolved chromosomes 5–9, Fig. 5A). The Tz745 has a distinct chromosome 12 var2csa locus and at least one and quite possibly two additional hybridizing loci in the poorly resolved chromosome 5–9 region (Fig. 5B).


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)

Chromosomal location of var2csa-type loci in P.falciparum isolates.Conditions for the separation of the chromosomes and DIG labeling and detection of the var2csa DBL3X domain-derived probe sequence are given in the Materials and Methods. Gel measuring rulers and superimposed alignment lines are shown. Marker chromosomes are from Hansenula wingei. Note that the two uppermost faint bands are not chromosomes but a PFG artifact. HB3, 3D7, FCR3/It4 and 7G8 are long term laboratory isolates whilst Tz745, Tz748, Tz752, Tz755, Tz788 and Tz796 are recent field isolates from Korogwe, Tanzania.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006667-g005: Chromosomal location of var2csa-type loci in P.falciparum isolates.Conditions for the separation of the chromosomes and DIG labeling and detection of the var2csa DBL3X domain-derived probe sequence are given in the Materials and Methods. Gel measuring rulers and superimposed alignment lines are shown. Marker chromosomes are from Hansenula wingei. Note that the two uppermost faint bands are not chromosomes but a PFG artifact. HB3, 3D7, FCR3/It4 and 7G8 are long term laboratory isolates whilst Tz745, Tz748, Tz752, Tz755, Tz788 and Tz796 are recent field isolates from Korogwe, Tanzania.
Mentions: Figure 5 illustrates a separation of the 14 P.falciparum chromosomes and the corresponding Southern blot, probed with a DBL3X-derived var2csa-specific gene probe. To compensate for gel distortions each sample was run in duplicate. The PFG illustrates the chromosome length polymorphisms that are a feature of P.falciparum [49]. Confirming earlier experiments, chromosome 12 contains a var2csa gene locus, hybridized by the var2csa gene probe in all 10 isolates shown in Figure 5. Two of the isolates, HB3 and Tz748, have one additional locus hybridizing the var2csa probe, on chromosome 1 in HB3 and on what is probably chromosome 8 in Tz748 (hybridizing to the upper region of the poorly resolved chromosomes 5–9, Fig. 5A). The Tz745 has a distinct chromosome 12 var2csa locus and at least one and quite possibly two additional hybridizing loci in the poorly resolved chromosome 5–9 region (Fig. 5B).

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