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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

Schematic representation of head-to-head genomic organisation of rif and upsA flanked var genes. Nine genes are flanked by a rif gene, which has its initiation codon approximately 3 or 4 kb upstream from the var initiation codon, and one var gene by another var gene at -2 kb. Punctured lines represent upsA, dotted lines upsA-rif and full line upsBsh. The diamond marks the putative termination site of upsA characterised by a stretch of TA repeats. Sizes of genes are not in scale.
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Figure 1: Schematic representation of head-to-head genomic organisation of rif and upsA flanked var genes. Nine genes are flanked by a rif gene, which has its initiation codon approximately 3 or 4 kb upstream from the var initiation codon, and one var gene by another var gene at -2 kb. Punctured lines represent upsA, dotted lines upsA-rif and full line upsBsh. The diamond marks the putative termination site of upsA characterised by a stretch of TA repeats. Sizes of genes are not in scale.

Mentions: Ten var genes had 5' regions belonging to this group and all but one were positioned head-to-head with a rif gene, the exception PF08_0141 was head-to-head with another var gene (figure 1). The distance from the start codons of the var to the rif gene was either 3 or 4 kb. From the var gene translation initiation codon to about 1.2 kb upstream the ten sequences were almost identical up to a stretch of TA repeats, which we propose identifies the 5' end of the upsA. This conclusion is based on analysis of the sequences further upstream from the TA repeats, which probably identifies 5' regions of the neighbouring genes. Thus, six sequences were almost identical until the translation initiation codon of the flanking rif gene. Another group of three sequences also shared this similarity but had an insertion of around 1 kb at the proposed upsA end. Characteristic of this group is that the PfEMP1s consist of only two DBL domains. The last sequence flanking PF08_0141 constitutes the upstream region of another var gene.


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)

Schematic representation of head-to-head genomic organisation of rif and upsA flanked var genes. Nine genes are flanked by a rif gene, which has its initiation codon approximately 3 or 4 kb upstream from the var initiation codon, and one var gene by another var gene at -2 kb. Punctured lines represent upsA, dotted lines upsA-rif and full line upsBsh. The diamond marks the putative termination site of upsA characterised by a stretch of TA repeats. Sizes of genes are not in scale.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC222925&req=5

Figure 1: Schematic representation of head-to-head genomic organisation of rif and upsA flanked var genes. Nine genes are flanked by a rif gene, which has its initiation codon approximately 3 or 4 kb upstream from the var initiation codon, and one var gene by another var gene at -2 kb. Punctured lines represent upsA, dotted lines upsA-rif and full line upsBsh. The diamond marks the putative termination site of upsA characterised by a stretch of TA repeats. Sizes of genes are not in scale.
Mentions: Ten var genes had 5' regions belonging to this group and all but one were positioned head-to-head with a rif gene, the exception PF08_0141 was head-to-head with another var gene (figure 1). The distance from the start codons of the var to the rif gene was either 3 or 4 kb. From the var gene translation initiation codon to about 1.2 kb upstream the ten sequences were almost identical up to a stretch of TA repeats, which we propose identifies the 5' end of the upsA. This conclusion is based on analysis of the sequences further upstream from the TA repeats, which probably identifies 5' regions of the neighbouring genes. Thus, six sequences were almost identical until the translation initiation codon of the flanking rif gene. Another group of three sequences also shared this similarity but had an insertion of around 1 kb at the proposed upsA end. Characteristic of this group is that the PfEMP1s consist of only two DBL domains. The last sequence flanking PF08_0141 constitutes the upstream region of another var gene.

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