The polymorphic 11.1 locus of Plasmodium falciparum

Kahane, Bernard; Sibilli, Lise; Scherf, Artur; Jaureguiberry, Ginette; Langsley, Gordon; Ozaki, Luiz Shozo; Guillotte, Micheline; Müller‐Hill, Benno; Silva, Luis Pereira da; Mercereau‐Puijalon, Odile

doi:10.1016/0166-6851(87)90132-0

Cited by 20 publications

(14 citation statements)

References 29 publications

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“…The PflJ -J gene of P.falciparum is a large locus (> 30 kb) with a nucleotide sequence that predicts a glutamic acid-rich polypeptide containing three blocks of tandem repeats of three, six and nine amino acids (Kahane et al, 1987;Scherf et al, 1988). The structure, function and cellular location of the Pfl 1-1 protein have been difficult to determine because of immunological cross-reactivity between putative Pfl -1 proteins and other malarial proteins.…”

Section: Resultsmentioning

confidence: 99%

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Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

et al. 1992

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We report the identification of the product of the Plasmodium falciparum Pf11‐1 gene and demonstrate that it is a gametocyte‐specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11‐1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid‐rich polypeptide. Our identification of the Pf11‐1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11‐1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR‐based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11‐1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11‐1 gene‐specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11‐1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11‐1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11‐1 in erythrocyte rupture within the mosquito gut.

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Section: Resultsmentioning

confidence: 99%

“…The parasite strains used in this work, Banjul (Gambia), FCC1 (China), ITG2G1 (Brazil), T996 (Thailand), FCR3 (West Africa) and Palo Alto (Uganda) were described by Kahane et al (1987); 3D7 is a clone with high capacity for gametocyte production derived from NF54 as described by Walliker et al (1987).…”

Section: Discussionmentioning

confidence: 99%

Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

et al. 1992

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“…Another gene that was over amplified, PF10_0374 that codes for a large gametocyte-expressed protein Pf11-1 and has 10 probes, had multiple probes that displayed over amplification. This gene contains a repetitive sequence that evolves rapidly to produce strain variation [136]–[138] and which is also found in other antigens (antigen 332 PF11_0507 and RESA). Thus the expression differences based on this gene should be considered unreliable, as supported by discrepant results for this gene in 3D7 from other studies [50],[58].…”

Section: Supporting Informationmentioning

confidence: 99%

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates

et al. 2009

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Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted field isolates of Plasmodium falciparum, the species responsible for most malarial disease. It was found that genes coding for parasite protein export into the red cell cytosol and onto its surface, and genes coding for sexual stage proteins involved in parasite transmission are up-regulated in field isolates compared with long-term laboratory isolates. Much of this variability was associated with the loss of small or large chromosomal segments, or other forms of gene copy number variation that are prevalent in the P. falciparum genome (copy number variants, CNVs). Expression levels of genes inside these segments were correlated to that of genes outside and adjacent to the segment boundaries, and this association declined with distance from the CNV boundary. This observation could not be explained by copy number variation in these adjacent genes. This suggests a local-acting regulatory role for CNVs in transcription of neighboring genes and helps explain the chromosomal clustering that we observed here. Transcriptional co-regulation of physical clusters of adaptive genes may provide a way for the parasite to readily adapt to its highly heterogeneous and strongly selective environment.

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“…In contrast to the 11-1.5' region we find extreme RFLPs in the divergent R9 repeats of the 11-1 locus (see Figure 6B and Kahane et al, 1987).…”

Section: R9 Repeatsmentioning

confidence: 65%

“…The similar restriction pattern of two parts of the 11-1 locus (Kahane et al, 1987) suggested that it may consist of two duplicated genes, as has been proposed for the P.falciparum genes PfHRP-II/III and DHFR-TS (Wellems and Howard, 1986;Inselburg et al, 1987). We investigated whether the region 5' to the region R9 had also been duplicated.…”

Section: Organization Of the 1 1-1 Locusmentioning

confidence: 76%

The 11-1 gene of Plasmodium falciparum codes for distinct fast evolving repeats.

Scherf

Hilbich²,

Sieg³

et al. 1988

The EMBO Journal

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The 11‐1 gene of Plasmodium falciparum has been investigated by DNA sequence analysis. It begins at the 5′ end with a putative miniexon coding for a polypeptide which has the characteristics of a signal sequence. The miniexon is followed by a small intron. This again is followed by a large exon consisting of 9‐, 18‐ and 27‐bp repeats embedded in unique DNA. Specific antibodies isolated by affinity chromatography on a purified recombinant fusion protein expressing the three‐ and six‐amino acid repeats were used to identify the product of the 11‐1 gene. In exhibits size variations from 260 to 350 kd in different strains. Southern blot analysis with synthetic DNA as probe demonstrates that the 18‐bp repeat is absent or drastically altered in two strains whereas the other repeats are present in all seven strains investigated. The unusual preference for G in the third position of some codons of the repeats but not in the unique sequences indicates rapid evolution of the repeats. Slippage during replication, unequal crossing over and selection are discussed as possible mechanisms leading rapidly to extreme diversity.

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The polymorphic 11.1 locus of Plasmodium falciparum

Cited by 20 publications

References 29 publications

Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates

The 11-1 gene of Plasmodium falciparum codes for distinct fast evolving repeats.

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