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Analysis of Plasmodium falciparum PfEMP-1/var genes suggests that recombination rearranges constrained sequences
C P Ward1, G T Clottey, M Dorris
1Institute of Cell, Animal and Population Biology, Division of Biology, University of Edinburgh, Scotland, UK.
Abstract:
The var genes of Plasmodium falciparum encode a family of parasite erythrocyte surface antigens, the PfEMP-1 proteins, which function as adhesion ligands for host endothelial and erythrocyte receptors. PfEMP-1 is extremely polymorphic although the extent of this variation in naturally transmitted parasite populations is unclear. We have identified 56 different sequences from the Duffy binding-like (DBL-1) domain of var genes amplified from six different P. falciparum clones isolated from patient infections in a Sudanese village in October-November 1989. These clones have been compared with 25 PfEMP-1 sequences expressed from different var gene loci by the 3D7A clone and 48 PfEMP-1 sequences from different isolates in endemic areas such as Kenya, Brazil, Gambia, Vietnam and Vanuatu to analyse diversity in clonal, local and 'global' P. falciparum populations. Evidence that certain conserved sequences recur in clones from one Sudanese village and in isolates from all over the world suggests that var gene diversity is the result of recombinational reshuffling of a subset of conserved, presumably ancestral sequences. Recurrence of particular var sequence blocks thus leads to 'overlaps' in the PfEMP-1 sequence repertoire of different P. falciparum clones.
Insights
The Plasmodium falciparum var gene family, encoding PfEMP-1 proteins, shows extensive sequence variation. Conserved sequences recur globally, suggesting recombinational shuffling of ancestral sequences drives var gene diversity.
Area of Science:
- Genetics
- Parasitology
- Molecular Biology
Background:
- The Plasmodium falciparum var genes encode PfEMP-1 proteins, crucial for parasite adhesion to host cells.
- PfEMP-1 exhibits extreme polymorphism, but the extent of variation in natural parasite populations remains largely unknown.
Purpose of the Study:
- To analyze the diversity of var genes in Plasmodium falciparum populations.
- To investigate the evolutionary mechanisms driving var gene sequence variation.
Main Methods:
- Amplification of Duffy binding-like (DBL-1) domain sequences from var genes of six P. falciparum clones from Sudan.
- Comparison of these sequences with existing PfEMP-1 sequences from various global isolates and the 3D7A clone.
Main Results:
- Identification of 56 distinct DBL-1 domain sequences from Sudanese P. falciparum clones.
- Evidence of recurring conserved sequences in both local Sudanese clones and global P. falciparum isolates.
- Observed 'overlaps' in the PfEMP-1 sequence repertoire across different P. falciparum clones.
Conclusions:
- Var gene diversity in Plasmodium falciparum is shaped by the recombinational shuffling of conserved, ancestral sequences.
- Recurring sequence blocks contribute to the overlapping PfEMP-1 repertoire among different parasite clones.