Limits...
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.

Show MeSH

Related in: MedlinePlus

Distance tree of all 3D7 DBLx and randomly chosen 50 DBL domains representing all DBL subtypes generated using the p-distance/NJ method. All clusters were supported by their bootstrap proportions and by maximum parsimony tree making method (data not shown) Numbers at the nodes represent bootstrap proportions (BP) on 1000 replicates. The scale bar represents the proportion of different amino acids compared. PlasmoDB accession numbers are shown.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC222925&req=5

Figure 5: Distance tree of all 3D7 DBLx and randomly chosen 50 DBL domains representing all DBL subtypes generated using the p-distance/NJ method. All clusters were supported by their bootstrap proportions and by maximum parsimony tree making method (data not shown) Numbers at the nodes represent bootstrap proportions (BP) on 1000 replicates. The scale bar represents the proportion of different amino acids compared. PlasmoDB accession numbers are shown.

Mentions: Among the var genes of 3D7 PFL0030c (var2) differs markedly with respect to domain structure and 5' region. The gene does not encode a CIDR domain and of the six encoded DBL domains, three have previously been classified as DBLx [17], indicating that they along with ten other DBL domains did not fit into the existing classification by Smith et al. [16]. In attempt to classify these domains we randomly choose 50 DBL domains to represent DBLα-ε and figure 5 shows a tree of these together with the DBLx domains. Although the analysis was based on 3D7 sequences only and cannot be considered definitive some patterns emerged. The DBL1x domain was seen as a side branch to DBLα cluster. The var2 DBL2x and DBL3x domains did not fall into any of the clusters, but was most closely related to the DBLε sequences. Of the ten other DBLx domains, three formed a separate cluster, which in this study were named DBLζ. These DBLζ domains were part of PfEMP1s with identical domain structure. Six DBLx domains fell within or clustered closely to DBLδs. Like other DBLδ they were flanked by a CIDR domain, and were classified as DBLδ in figure 7. One DBLx domain clustered with DBLγ sequences and was classified as such in figure 7.


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 all 3D7 DBLx and randomly chosen 50 DBL domains representing all DBL subtypes generated using the p-distance/NJ method. All clusters were supported by their bootstrap proportions and by maximum parsimony tree making method (data not shown) Numbers at the nodes represent bootstrap proportions (BP) on 1000 replicates. The scale bar represents the proportion of different amino acids compared. PlasmoDB accession numbers are shown.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Distance tree of all 3D7 DBLx and randomly chosen 50 DBL domains representing all DBL subtypes generated using the p-distance/NJ method. All clusters were supported by their bootstrap proportions and by maximum parsimony tree making method (data not shown) Numbers at the nodes represent bootstrap proportions (BP) on 1000 replicates. The scale bar represents the proportion of different amino acids compared. PlasmoDB accession numbers are shown.
Mentions: Among the var genes of 3D7 PFL0030c (var2) differs markedly with respect to domain structure and 5' region. The gene does not encode a CIDR domain and of the six encoded DBL domains, three have previously been classified as DBLx [17], indicating that they along with ten other DBL domains did not fit into the existing classification by Smith et al. [16]. In attempt to classify these domains we randomly choose 50 DBL domains to represent DBLα-ε and figure 5 shows a tree of these together with the DBLx domains. Although the analysis was based on 3D7 sequences only and cannot be considered definitive some patterns emerged. The DBL1x domain was seen as a side branch to DBLα cluster. The var2 DBL2x and DBL3x domains did not fall into any of the clusters, but was most closely related to the DBLε sequences. Of the ten other DBLx domains, three formed a separate cluster, which in this study were named DBLζ. These DBLζ domains were part of PfEMP1s with identical domain structure. Six DBLx domains fell within or clustered closely to DBLδs. Like other DBLδ they were flanked by a CIDR domain, and were classified as DBLδ in figure 7. One DBLx domain clustered with DBLγ sequences and was classified as such in figure 7.

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