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9 Population Structure and Recent Evolution of Plasmodium falciparum
Pages 143-164

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From page 143...
... Abbreviations: CSP, circumsporozoite protein; MSP-1 and MSP-2, merozoite surface proteins 1 and 2, respectively; CR, central region; NR, not repetitive; RAT, repeat allotype; RHR, repeat homology region.
From page 144...
... We conclude that the antigenic polymorphisms are consistent with the recent origin of the world populations of P falciparum inferred from the analysis of nonantigenic genes.
From page 145...
... It seems paradoxical that P falciparum antigenic genes would be so highly polymorphic, because these genes must have shared the recent allelic homogenization caused by the population bottleneck we have inferred.
From page 146...
... 1 100 berghei 1 100 ~= /ii 1 r berghei2 —yce/ii 2 FIGURE 1. Phylogeny of 12 Plasmodium species inferred from Csp gene sequences.
From page 147...
... one or more recent selective sweeps affecting the genome as a whole, and (v) a demographic sweep, i.e., a recent population bottleneck, so that extant world populations of P
From page 148...
... 148 CD CD $= so :^ .~ o to CD s~ ~ o o ~ ~ o ~ $' o ~ :^ o .= o .
From page 149...
... falciparum is recent and has come about, in part, as a consequence of a recent dramatic rise in vectorial capacity caused by repeated speciation events in Africa of the most anthropophilic members of the species complexes of the Anopheles gambiae and Anophelesfunestus mosquito vectors. The biological processes implied by this account may have, in turn, been associated with, and even depended on the onset of agricultural societies in Africa and climatic changes, specifically the gradual increase in ambient temperatures after the Wurm glaciation, so that about 6,000 years ago climatic conditions in the Mediterranean region and the Middle East made possible the spread of P
From page 150...
... We will show that some of the reported nucleotide variation between antigenic alleles is an artifact stemming from misalignment of gene sequences that are of different lengths as a consequence of unequal numbers of repetitions generated by intragenic recombination. THE CSP GENE The Csp gene is comprised of two terminal regions that are not repetitive (5' NR and 3' NR)
From page 151...
... to refer to variant nucleotide sequences that encode a single amino acid motif (Rich et al., 1997~. Among the known Csp gene sequences of P.falciparum, there are 10 RATs that encode the NANP motif and four RATs that encode the NVDP motif, with an average of about 10 RATs per gene sequence (range 9-11; see Table 6~.
From page 153...
... We have proposed that most of the variation in antigenic genes is attributable to duplication and/or deletion of the repeated segments within the genes, which is simply an instance of the general slippedstrand process for generating length variation in repetitive DNA regions (Fig.
From page 154...
... falciparum (Su and Wellems, 1996; Anderson et al., 1999~. However, intragenic recombination also has been implicated in generating variability within coding regions in a variety of eukaryotes; including the Drosophila yolk protein gene and the human oc2-globin gene, to cite just two examples (Ho et al., 1996; Oron-Karni et al., 1997~.
From page 155...
... 4~. The dimorphism observed among group I and II alleles within block 2 has been shown to result by processes analogous to those within the Csp central repeat region (Frontal)
From page 156...
... Alleles within and between groups are similar, except for occasional (mostly synonymous) substitutions and for differences generated by intragenic recombination, evidenced by the presence of repeats.
From page 157...
... falciparum antigenic variation. The observation of highly significant repeats within regions of the Msp-1 gene previously thought not to be repetitive makes it clear that the extensive between-group nucleotide diversity between the two allelic groups is attributable to the same kinds of repeat variation and rapid divergence known in other antigenic determinants.
From page 158...
... A closer look at the nucleotides within the central portion of the gene manifests the homology of three distinct regions, which we define as repeat homology regions (RHRs)
From page 159...
... Receipt Ht3~.~gy Peq§~n ~ ~.~ ~ Tat ac:tactact FIGURE 6. Partial nucleotide alignments of three Msp-2 gene sequences to manifest the repeats and the homologies between P
From page 160...
... As noted for Csp, the repetitive DNA sequences found within the aaligttCaa9~ct9gc,d,~bgoa3~aaa~a~,acaU.ac~q~g~Laagag~gaaaa scaaaaLgaa aaagtteas~ttote~3ga~cocat<:aaacaetaca~ag0,~.g~aegaggat~aaaacaaaaLgaa FIGURE 7. Nucleotide alignment of two Msp-2 gene sequences to manifest the repeats within RHR3 of P
From page 161...
... falciparum antigens. ANTIGENIC POLYMORPHISM, INTRAGENIC RECOMBINATION, AND POPULATION STRUCTURE Homologous comparisons among allelic variants of antigenic genes manifest that most of the variation is attributable to the rapid mutational processes associated with intragenic recombination.
From page 162...
... (1998) Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum.
From page 163...
... (1996) Phylogenetic relationship among the malaria parasites based on small subunit rRNA gene sequences: monophyletic nature of the human malaria parasite, Plasmodium falciparum.
From page 164...
... (1987) Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum.


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