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Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.

Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG - Malar. J. (2003)

Bottom Line: 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 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Medical Parasitology at Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark. thomaslavstsen@vip.cybercity.dk

ABSTRACT

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

Conclusion: 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.

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Related in: MedlinePlus

Distance tree of 3D7 RIFINs generated using the p-distance/NJ method. MAL6P1.251 was left out as it aligned closer to STEVORs in preliminary alignments (data not shown). Red dots mark RIFINs flanked by upsA-rif. Though, the tree topology could not be confirmed by bootstrapping, the clusters containing the marked RIFINs were verified by the maximum parsimony tree (not shown). The scale bar represents the proportion of different amino acids compared. No accession numbers are given to simplify the graphics.
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Figure 6: Distance tree of 3D7 RIFINs generated using the p-distance/NJ method. MAL6P1.251 was left out as it aligned closer to STEVORs in preliminary alignments (data not shown). Red dots mark RIFINs flanked by upsA-rif. Though, the tree topology could not be confirmed by bootstrapping, the clusters containing the marked RIFINs were verified by the maximum parsimony tree (not shown). The scale bar represents the proportion of different amino acids compared. No accession numbers are given to simplify the graphics.

Mentions: As described, all but one of the upsA sequences were flanked by a rif gene transcribed in the opposite direction and all of these rif genes appeared to share a 5' region, here named upsA-rif. rif genes exhibit a chromosomal organisation similar to var genes, i.e. a small subset genes including the upsA-rif flanked genes were found to be transcribed in direction opposite to the majority. Thus, the rif genes located near the telomere and transcribed towards the centromere were organised as one to three successive genes with the most 5' gene flanked by a sequence with high similarity to upsA-rif. Sequence analysis of 3D7 RIFINs revealed that 12 of 16 RIFINs with a upsA-rif grouped into two separate clusters (figure 6). BLAST search of randomly chosen 1.7 kb RIFIN 5' regions showed that other RIFIN clusters shared distinct upstream sequences (not shown).


Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.

Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG - Malar. J. (2003)

Distance tree of 3D7 RIFINs generated using the p-distance/NJ method. MAL6P1.251 was left out as it aligned closer to STEVORs in preliminary alignments (data not shown). Red dots mark RIFINs flanked by upsA-rif. Though, the tree topology could not be confirmed by bootstrapping, the clusters containing the marked RIFINs were verified by the maximum parsimony tree (not shown). The scale bar represents the proportion of different amino acids compared. No accession numbers are given to simplify the graphics.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC222925&req=5

Figure 6: Distance tree of 3D7 RIFINs generated using the p-distance/NJ method. MAL6P1.251 was left out as it aligned closer to STEVORs in preliminary alignments (data not shown). Red dots mark RIFINs flanked by upsA-rif. Though, the tree topology could not be confirmed by bootstrapping, the clusters containing the marked RIFINs were verified by the maximum parsimony tree (not shown). The scale bar represents the proportion of different amino acids compared. No accession numbers are given to simplify the graphics.
Mentions: As described, all but one of the upsA sequences were flanked by a rif gene transcribed in the opposite direction and all of these rif genes appeared to share a 5' region, here named upsA-rif. rif genes exhibit a chromosomal organisation similar to var genes, i.e. a small subset genes including the upsA-rif flanked genes were found to be transcribed in direction opposite to the majority. Thus, the rif genes located near the telomere and transcribed towards the centromere were organised as one to three successive genes with the most 5' gene flanked by a sequence with high similarity to upsA-rif. Sequence analysis of 3D7 RIFINs revealed that 12 of 16 RIFINs with a upsA-rif grouped into two separate clusters (figure 6). BLAST search of randomly chosen 1.7 kb RIFIN 5' regions showed that other RIFIN clusters shared distinct upstream sequences (not shown).

Bottom Line: 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 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Medical Parasitology at Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark. thomaslavstsen@vip.cybercity.dk

ABSTRACT

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

Conclusion: 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.

Show MeSH
Related in: MedlinePlus