Plasmodium falciparum: Dimorphism of the p190 alleles

Tanabe, Kazuyuki; Murakami, Kenji; Doi, Syuichi

doi:10.1016/0014-4894(89)90132-x

Cited by 12 publications

(8 citation statements)

References 19 publications

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“…This indicates that the gpl95 sequences of the two isolates shared this allelic block, which encodes a sequence of 30 amino acids. The sharing of allelic sequences within block 4 of FVO and FUP gpl95s is not unusual, since recombination between the gpl95 alleles is very common in this region and, as a result, parasite clones that harbor both gpl95 alleles and that share the same allelic sequences in block 4 have been found (45,46,57).…”

Section: Resultsmentioning

confidence: 99%

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Roles of conserved and allelic regions of the major merozoite surface protein (gp195) in immunity against Plasmodium falciparum

1992

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The Plasmodium falciparum major merozoite surface protein gp195 is a candidate antigen for a vaccine against human malaria. The significance of allelism and polymorphism in vaccine-induced immunity to gp195 was investigated in this study. Rabbits were immunized with each of two allelic forms of gp195 that were affinity purified from the FUP and FVO parasite isolates. gp195-specific antibodies raised against one allelic form of gp195 cross-reacted extensively with the gp195 of the heterologous allele in enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence assays. Competitive binding ELISAs with homologous and heterologous gpl95s confirmed that a majority of the anti-gp195 antibodies produced against either allelic protein were cross-reactive. Moreover, the biological activities of the gp195 antibody responses were also highly cross-reactive, since anti-gp195 sera inhibited the in vitro growth of the homologous and heterologous parasites with equal efficiency. The degree of cross-reactivity with strain-specific and allele-specific determinants of gp195 in the ELISA was low. These results suggest that the immunological cross-reactivity between the two gp195 proteins is due to recognition of conserved determinants. They also suggest that a gp195-based vaccine may be effective against blood-stage infection with a diverse array of parasite isolates.

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Section: Resultsmentioning

confidence: 99%

“…Thus, gp195 is a candidate human vaccine antigen against malaria. Genetic analyses of gpl95 from a number of parasite isolates indicate that gpl95 exists primarily in two allelic forms (56,57). Allele-specific sequences occur as segments or blocks along the gpl95 molecule and are flanked by conserved segments or blocks (56).…”

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confidence: 99%

Roles of conserved and allelic regions of the major merozoite surface protein (gp195) in immunity against Plasmodium falciparum

1992

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“…The data did not indicate any single ''hot spot'' of recombination in the msp1 gene, and disequilibrium was not particularly lower between sites separated by a highly polymorphic repeat sequence (within block 2 of the gene). Other studies have indicated that there is a ''cold spot'' for recombination in a 3.7-kb region of the gene, between blocks 6 and 16 in the scheme of Tanabe et al (17), in which there are two highly divergent dimorphic sequences and recombination appears to have occurred between haplotypes of the same, but not different, dimorphic types (18,19). In the present study, one of the block 6-16 dimorphic types was almost at fixation in most populations (MAD-like allele frequency Ͼ0.90), and recombination across this region of the gene was not apparently restricted (only 2͞52 tests for linkage disequilibrium were significant over distances of Ͼ1.0 kb, most of which spanned this block 6-16 sequence).…”

Section: Discussionmentioning

confidence: 99%

“…These conditions allowed clear and accurate discrimination between alleles, including those Table 1). Dashed lines under blocks 6-16 indicate that this whole region exists as either one of two highly divergent dimorphic sequence types, between which no recombinants have been detected (18,19); therefore, typing of a sequence at only one representative dimorphic site (in block 14) was performed. (17)] Bases that differ between allelic probes are in bold and underlined.…”

Section: Methodsmentioning

confidence: 99%

“…To study linkage disequilibrium in a statistically appropriate manner, larger population samples are necessary (16). Previous evidence for interallelic recombination in the msp1 (merozoite surface protein 1) antigen gene (17)(18)(19)(20) provided a basis for prospectively designing a study of linkage disequilibrium and molecular map distance. Here, 547 P. falciparum isolates from six populations in Africa (the continent with 90% of all P. falciparum infections) have been studied, with multiple polymorphic sites genotyped throughout the msp1 gene, covering a nucleotide distance of approximately 5 kb in a nontelomeric region of chromosome 9 (1).…”

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confidence: 99%

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High recombination rate in natural populations of Plasmodium falciparum

Conway

Roper

Oduola

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

263

162

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Malaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If meiotic recombination occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is expected to decline with increasing distance along a chromosome. The rate of this decline should be proportional to the effective meiotic recombination rate in the population. Multiple polymorphic sites covering a 5-kb region of chromosome 9 (the msp1 gene) have been typed in 547 isolates from six populations in Africa to test for such a decline and estimate its rate in populations of Plasmodium falciparum. The magnitude of two-site linkage disequilibrium declines markedly with increasing molecular map distance between the sites, reaching nonsignificant levels within a map range of 0.3-1.0 kb in five of the populations and over a larger map distance in the population with lowest malaria endemicity. The rate of decline in linkage disequilibrium over molecular map distance is at least as rapid as that observed in most chromosomal regions of other sexually reproducing eukaryotes, such as humans and Drosophila. These results are consistent with the effective recombination rate expected in natural populations of P. falciparum, predicted on the basis of the underlying molecular rate of meiotic crossover and the coefficient of inbreeding caused by self-fertilization events. This is conclusive evidence to reject any hypothesis of clonality or low rate of meiotic recombination in P. falciparum populations. Moreover, the data have major implications for the design and interpretation of population genetic studies of selection on P. falciparum genes.

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