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Genetic relatedness of Plasmodium falciparum isolates and the origin of allelic diversity at the merozoite surface protein-1 (MSP-1) locus in Brazil and Vietnam.

Hoffmann EH, Ribolla PE, Ferreira MU - Malar. J. (2003)

Bottom Line: At least one epidemic clone propagating in Brazil remained relatively unchanged over more than one decade.Moreover, we found no evidence that rearrangements of MSP-1 repeats, putatively created by mitotic recombination events, generated new alleles within clonal lineages of parasites in either country.Identical MSP-1 alleles originated from co-ancestry in both populations, whereas nearly identical MSP-1 alleles have probably appeared independently in unrelated parasite lineages.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, Brazil. hoffmann@usp.br

ABSTRACT

Background: Despite the extensive polymorphism at the merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum, that encodes a major repetitive malaria vaccine candidate antigen, identical and nearly identical alleles frequently occur in sympatric parasites. Here we used microsatellite haplotyping to estimate the genetic distance between isolates carrying identical and nearly identical MSP-1 alleles.

Methods: We analyzed 28 isolates from hypoendemic areas in north-western Brazil, collected between 1985 and 1998, and 23 isolates obtained in mesoendemic southern Vietnam in 1996. MSP-1 alleles were characterized by combining PCR typing with allele-specific primers and partial DNA sequencing. The following single-copy microsatellite markers were typed : Polyalpha, TA42 (only for Brazilian samples), TA81, TA1, TA87, TA109 (only for Brazilian samples), 2490, ARAII, PfG377, PfPK2, and TA60.

Results: The low pair-wise average genetic distance between microsatellite haplotypes of isolates sharing identical MSP-1 alleles indicates that epidemic propagation of discrete parasite clones originated most identical MSP-1 alleles in parasite populations from Brazil and Vietnam. At least one epidemic clone propagating in Brazil remained relatively unchanged over more than one decade. Moreover, we found no evidence that rearrangements of MSP-1 repeats, putatively created by mitotic recombination events, generated new alleles within clonal lineages of parasites in either country.

Conclusion: Identical MSP-1 alleles originated from co-ancestry in both populations, whereas nearly identical MSP-1 alleles have probably appeared independently in unrelated parasite lineages.

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Fitch-Margoliash tree showing the relationships between 11-locus microsatellite haplotypes in 28 Plasmodium falciparum isolates from Brazil. MSP-1 alleles (numbered according to Fig. 1B) and dates of collection are also shown.
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Figure 2: Fitch-Margoliash tree showing the relationships between 11-locus microsatellite haplotypes in 28 Plasmodium falciparum isolates from Brazil. MSP-1 alleles (numbered according to Fig. 1B) and dates of collection are also shown.

Mentions: The number of alleles at each microsatellite locus in Brazilian isolates ranged between 2 and 5 (average, 2.64), with relative low estimates of expected heterozygosity (0.14–0.49; average, 0.38) (Table 1). Most Brazilian isolates sharing identical MSP-1 alleles tended to cluster together in the Fitch-Margoliash tree based on pair-wise genetic distances of 11-locus microsatellite haplotypes (Figure 2). Three out of four groups of Brazilian isolates with identical multilocus haplotypes (as indicated by the zero length of terminal branches in the tree) comprised parasites sharing identical MSP-1 alleles collected during the same decade. The average genetic distance of isolates sharing identical MSP-1 alleles (0.304; 50 pair-wise comparisons) was significantly lower (P < 0.0001) than that estimated for isolates with different MSP-1 alleles (0.431; 328 pair-wise comparisons). Microsatellite data thus indicate that most identical MSP-1 alleles in this population occurred in genetically related parasites, possibly due to the epidemic propagation of a few discrete parasite lineages. Moreover, they suggest that at least one of these epidemic lineages changed little over more than one decade, since isolates sharing the MSP-1 allele #34 which were collected both in 1985 (RO37 and RO41) and 1998 (13OC) clustered together in the tree (Figure 2).


Genetic relatedness of Plasmodium falciparum isolates and the origin of allelic diversity at the merozoite surface protein-1 (MSP-1) locus in Brazil and Vietnam.

Hoffmann EH, Ribolla PE, Ferreira MU - Malar. J. (2003)

Fitch-Margoliash tree showing the relationships between 11-locus microsatellite haplotypes in 28 Plasmodium falciparum isolates from Brazil. MSP-1 alleles (numbered according to Fig. 1B) and dates of collection are also shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC184523&req=5

Figure 2: Fitch-Margoliash tree showing the relationships between 11-locus microsatellite haplotypes in 28 Plasmodium falciparum isolates from Brazil. MSP-1 alleles (numbered according to Fig. 1B) and dates of collection are also shown.
Mentions: The number of alleles at each microsatellite locus in Brazilian isolates ranged between 2 and 5 (average, 2.64), with relative low estimates of expected heterozygosity (0.14–0.49; average, 0.38) (Table 1). Most Brazilian isolates sharing identical MSP-1 alleles tended to cluster together in the Fitch-Margoliash tree based on pair-wise genetic distances of 11-locus microsatellite haplotypes (Figure 2). Three out of four groups of Brazilian isolates with identical multilocus haplotypes (as indicated by the zero length of terminal branches in the tree) comprised parasites sharing identical MSP-1 alleles collected during the same decade. The average genetic distance of isolates sharing identical MSP-1 alleles (0.304; 50 pair-wise comparisons) was significantly lower (P < 0.0001) than that estimated for isolates with different MSP-1 alleles (0.431; 328 pair-wise comparisons). Microsatellite data thus indicate that most identical MSP-1 alleles in this population occurred in genetically related parasites, possibly due to the epidemic propagation of a few discrete parasite lineages. Moreover, they suggest that at least one of these epidemic lineages changed little over more than one decade, since isolates sharing the MSP-1 allele #34 which were collected both in 1985 (RO37 and RO41) and 1998 (13OC) clustered together in the tree (Figure 2).

Bottom Line: At least one epidemic clone propagating in Brazil remained relatively unchanged over more than one decade.Moreover, we found no evidence that rearrangements of MSP-1 repeats, putatively created by mitotic recombination events, generated new alleles within clonal lineages of parasites in either country.Identical MSP-1 alleles originated from co-ancestry in both populations, whereas nearly identical MSP-1 alleles have probably appeared independently in unrelated parasite lineages.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, Brazil. hoffmann@usp.br

ABSTRACT

Background: Despite the extensive polymorphism at the merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum, that encodes a major repetitive malaria vaccine candidate antigen, identical and nearly identical alleles frequently occur in sympatric parasites. Here we used microsatellite haplotyping to estimate the genetic distance between isolates carrying identical and nearly identical MSP-1 alleles.

Methods: We analyzed 28 isolates from hypoendemic areas in north-western Brazil, collected between 1985 and 1998, and 23 isolates obtained in mesoendemic southern Vietnam in 1996. MSP-1 alleles were characterized by combining PCR typing with allele-specific primers and partial DNA sequencing. The following single-copy microsatellite markers were typed : Polyalpha, TA42 (only for Brazilian samples), TA81, TA1, TA87, TA109 (only for Brazilian samples), 2490, ARAII, PfG377, PfPK2, and TA60.

Results: The low pair-wise average genetic distance between microsatellite haplotypes of isolates sharing identical MSP-1 alleles indicates that epidemic propagation of discrete parasite clones originated most identical MSP-1 alleles in parasite populations from Brazil and Vietnam. At least one epidemic clone propagating in Brazil remained relatively unchanged over more than one decade. Moreover, we found no evidence that rearrangements of MSP-1 repeats, putatively created by mitotic recombination events, generated new alleles within clonal lineages of parasites in either country.

Conclusion: Identical MSP-1 alleles originated from co-ancestry in both populations, whereas nearly identical MSP-1 alleles have probably appeared independently in unrelated parasite lineages.

Show MeSH