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A highly conserved segmental duplication in the subtelomeres of Plasmodium falciparum chromosomes varies in copy number.

Mok BW, Ribacke U, Sherwood E, Wahlgren M - Malar. J. (2008)

Bottom Line: The n-gene transcription levels were found to correlate to the number of n-gene copies.Fragments of SD1 harbouring two or three of the SD1-genes (o-gene, pfmc-2tm, q-gene) were also found in the 3D7 genome.In addition a related second SD, SD2, of approximately 55% sequence identity to SD1 was found duplicated in a fresh clinical isolate but was only present in a single copy in 3D7 and in other P. falciparum lines or clones.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, SE-171 77 Stockholm, Sweden. bobo.mok@ki.se

ABSTRACT

Background: Segmental duplications (SD) have been found in genomes of various organisms, often accumulated at the ends of chromosomes. It has been assumed that the sequence homology in-between the SDs allow for ectopic interactions that may contribute to the emergence of new genes or gene variants through recombinatorial events.

Methods: In silico analysis of the 3D7 Plasmodium falciparum genome, conducted to investigate the subtelomeric compartments, led to the identification of subtelomeric SDs. Sequence variation and copy number polymorphisms of the SDs were studied by DNA sequencing, real-time quantitative PCR (qPCR) and fluorescent in situ hybridization (FISH). The levels of transcription and the developmental expression of copy number variant genes were investigated by qPCR.

Results: A block of six genes of >10 kilobases in size, including var, rif, pfmc-2tm and three hypothetical genes (n-, o- and q-gene), was found duplicated in the subtelomeric regions of chromosomes 1, 2, 3, 6, 7, 10 and 11 (SD1). The number of SD1 per genome was found to vary from 4 to 8 copies in between different parasites. The intragenic regions of SD1 were found to be highly conserved across ten distinct fresh and long-term cultivated P. falciparum. Sequence variation was detected in a approximately 23 amino-acid long hypervariable region of a surface-exposed loop of PFMC-2TM. A hypothetical gene within SD1, the n-gene, encoding a PEXEL/VTS-containing two-transmembrane protein was found expressed in ring stage parasites. The n-gene transcription levels were found to correlate to the number of n-gene copies. Fragments of SD1 harbouring two or three of the SD1-genes (o-gene, pfmc-2tm, q-gene) were also found in the 3D7 genome. In addition a related second SD, SD2, of approximately 55% sequence identity to SD1 was found duplicated in a fresh clinical isolate but was only present in a single copy in 3D7 and in other P. falciparum lines or clones.

Conclusion: Plasmodium falciparum carries multiple sequence conserved SDs in the otherwise highly variable subtelomeres of its chromosomes. The uniqueness of the SDs amongst plasmodium species, and the conserved nature of the genes within, is intriguing and suggests an important role of the SD to P. falciparum.

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High-resolution display of gene families in the subtelomeric compartment of P. falciparum 3D7. Subtelomeric genes are plotted according to their chromosomal positions and color labeled. For additional information see Additional File 1. The 8 segmental duplications SD1 are located in the subtelomeres of multiple chromosomes, and are here depicted in pink shaded ellipses. A second segmental duplication on chromosome 1 named SD2 is marked with a pale blue shaded ellipse.
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Figure 1: High-resolution display of gene families in the subtelomeric compartment of P. falciparum 3D7. Subtelomeric genes are plotted according to their chromosomal positions and color labeled. For additional information see Additional File 1. The 8 segmental duplications SD1 are located in the subtelomeres of multiple chromosomes, and are here depicted in pink shaded ellipses. A second segmental duplication on chromosome 1 named SD2 is marked with a pale blue shaded ellipse.

Mentions: A graphical output of all genes in the subtelomeric block 4–5 for all 14 chromosomes was generated (Figure 1). The boundaries of the subtelomeric ends were defined based on the whole genome synteny mapping of P. falciparum with rodent malaria parasites (P. berghei, P. chabaudi and P. yoelii) [18]. Subtelomeric gene-families are categorized into 18 groups (Additional File 1) and are displayed in different colors. Grouping of the subtelomeric genes was based on information from literature, the OrthoMCL Database [39] and/or protein features (possession of PEXEL/VTS domain and transmembrane regions) acquired from the Plasmodium database [36] where protein domains were predicted using HMM against the Pfam database, version 17.


A highly conserved segmental duplication in the subtelomeres of Plasmodium falciparum chromosomes varies in copy number.

Mok BW, Ribacke U, Sherwood E, Wahlgren M - Malar. J. (2008)

High-resolution display of gene families in the subtelomeric compartment of P. falciparum 3D7. Subtelomeric genes are plotted according to their chromosomal positions and color labeled. For additional information see Additional File 1. The 8 segmental duplications SD1 are located in the subtelomeres of multiple chromosomes, and are here depicted in pink shaded ellipses. A second segmental duplication on chromosome 1 named SD2 is marked with a pale blue shaded ellipse.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2279139&req=5

Figure 1: High-resolution display of gene families in the subtelomeric compartment of P. falciparum 3D7. Subtelomeric genes are plotted according to their chromosomal positions and color labeled. For additional information see Additional File 1. The 8 segmental duplications SD1 are located in the subtelomeres of multiple chromosomes, and are here depicted in pink shaded ellipses. A second segmental duplication on chromosome 1 named SD2 is marked with a pale blue shaded ellipse.
Mentions: A graphical output of all genes in the subtelomeric block 4–5 for all 14 chromosomes was generated (Figure 1). The boundaries of the subtelomeric ends were defined based on the whole genome synteny mapping of P. falciparum with rodent malaria parasites (P. berghei, P. chabaudi and P. yoelii) [18]. Subtelomeric gene-families are categorized into 18 groups (Additional File 1) and are displayed in different colors. Grouping of the subtelomeric genes was based on information from literature, the OrthoMCL Database [39] and/or protein features (possession of PEXEL/VTS domain and transmembrane regions) acquired from the Plasmodium database [36] where protein domains were predicted using HMM against the Pfam database, version 17.

Bottom Line: The n-gene transcription levels were found to correlate to the number of n-gene copies.Fragments of SD1 harbouring two or three of the SD1-genes (o-gene, pfmc-2tm, q-gene) were also found in the 3D7 genome.In addition a related second SD, SD2, of approximately 55% sequence identity to SD1 was found duplicated in a fresh clinical isolate but was only present in a single copy in 3D7 and in other P. falciparum lines or clones.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, SE-171 77 Stockholm, Sweden. bobo.mok@ki.se

ABSTRACT

Background: Segmental duplications (SD) have been found in genomes of various organisms, often accumulated at the ends of chromosomes. It has been assumed that the sequence homology in-between the SDs allow for ectopic interactions that may contribute to the emergence of new genes or gene variants through recombinatorial events.

Methods: In silico analysis of the 3D7 Plasmodium falciparum genome, conducted to investigate the subtelomeric compartments, led to the identification of subtelomeric SDs. Sequence variation and copy number polymorphisms of the SDs were studied by DNA sequencing, real-time quantitative PCR (qPCR) and fluorescent in situ hybridization (FISH). The levels of transcription and the developmental expression of copy number variant genes were investigated by qPCR.

Results: A block of six genes of >10 kilobases in size, including var, rif, pfmc-2tm and three hypothetical genes (n-, o- and q-gene), was found duplicated in the subtelomeric regions of chromosomes 1, 2, 3, 6, 7, 10 and 11 (SD1). The number of SD1 per genome was found to vary from 4 to 8 copies in between different parasites. The intragenic regions of SD1 were found to be highly conserved across ten distinct fresh and long-term cultivated P. falciparum. Sequence variation was detected in a approximately 23 amino-acid long hypervariable region of a surface-exposed loop of PFMC-2TM. A hypothetical gene within SD1, the n-gene, encoding a PEXEL/VTS-containing two-transmembrane protein was found expressed in ring stage parasites. The n-gene transcription levels were found to correlate to the number of n-gene copies. Fragments of SD1 harbouring two or three of the SD1-genes (o-gene, pfmc-2tm, q-gene) were also found in the 3D7 genome. In addition a related second SD, SD2, of approximately 55% sequence identity to SD1 was found duplicated in a fresh clinical isolate but was only present in a single copy in 3D7 and in other P. falciparum lines or clones.

Conclusion: Plasmodium falciparum carries multiple sequence conserved SDs in the otherwise highly variable subtelomeres of its chromosomes. The uniqueness of the SDs amongst plasmodium species, and the conserved nature of the genes within, is intriguing and suggests an important role of the SD to P. falciparum.

Show MeSH
Related in: MedlinePlus