Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.
BACKGROUND
The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence.


METHODS
Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains.


RESULTS
var genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique for the group A var genes


CONCLUSIONS
The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.
Lavstsen
Thomas
T
Centre for Medical Parasitology at Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark. thomaslavstsen@vip.cybercity.dk
Salanti
Ali
A
Jensen
Anja T R
AT
Arnot
David E
DE
Theander
Thor G
TG
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D003001:Cloning, Molecular; D021901:DNA, Intergenic / Q000235:genetics*; D004910:Erythrocyte Membrane / Q000235:genetics; D005091:Exons / Q000235:genetics*; D014644:Genetic Variation; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D011544:Pseudogenes; D017422:Sequence Analysis, DNA / Q000379:methods
D000953:Antigens, Protozoan; D021901:DNA, Intergenic; D008565:Membrane Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum