@article {784,
	title = {Genetic variation and the recent worldwide expansion of Plasmodium falciparum.},
	journal = {Gene},
	volume = {261},
	year = {2000},
	month = {2000 Dec 30},
	pages = {161-70},
	abstract = {Plasmodium falciparum, the agent of human malignant malaria, diverged from Plasmodium reichenowi, the chimpanzee parasite, about the time the human and chimpanzee lineages diverged from each other. The absence of synonymous nucleotide variation at ten loci indicates that the world populations of P. falciparum derive most recently from one single strain, or {\textquoteright}cenancestor,{\textquoteright} which lived a few thousand years ago. Antigenic genes of P. falciparum (such as Csp, Msp-1, and Msp-2) exhibit numerous polymorphisms that have been estimated to be millions of years old. We have discovered in these antigenic genes short repetitive sequences that distort the alignment of alleles and account for the apparent old age of the polymorphisms. The processes of intragenic recombination that generate the repeats occur at rates about 10(-3) to 10(-2), several orders of magnitude greater than the typical mutational process of nucleotide substitutions. We conclude that the antigenic polymorphisms of P. falciparum are consistent with a recent expansion of the world populations of the parasite from a cenancestor that lived in tropical Africa a few thousand years ago.},
	keywords = {Animals, Antigens, Protozoan, Base Sequence, Genetic Variation, Merozoite Surface Protein 1, Molecular Sequence Data, Phylogeny, Plasmodium, Plasmodium falciparum, Polymorphism, Genetic, Protozoan Proteins, Repetitive Sequences, Nucleic Acid, RNA, Ribosomal, Sequence Homology, Nucleic Acid, Species Specificity},
	issn = {0378-1119},
	author = {Ayala, F J and Rich, S M}
}
@article {793,
	title = {Malaria{\textquoteright}s Eve: evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {95},
	year = {1998},
	month = {1998 Apr 14},
	pages = {4425-30},
	abstract = {We have analyzed DNA sequences from world-wide geographic strains of Plasmodium falciparum and found a complete absence of synonymous DNA polymorphism at 10 gene loci. We hypothesize that all extant world populations of the parasite have recently derived (within several thousand years) from a single ancestral strain. The upper limit of the 95\% confidence interval for the time when this most recent common ancestor lived is between 24,500 and 57,500 years ago (depending on different estimates of the nucleotide substitution rate); the actual time is likely to be much more recent. The recent origin of the P. falciparum populations could have resulted from either a demographic sweep (P. falciparum has only recently spread throughout the world from a small geographically confined population) or a selective sweep (one strain favored by natural selection has recently replaced all others). The selective sweep hypothesis requires that populations of P. falciparum be effectively clonal, despite the obligate sexual stage of the parasite life cycle. A demographic sweep that started several thousand years ago is consistent with worldwide climatic changes ensuing the last glaciation, increased anthropophilia of the mosquito vectors, and the spread of agriculture. P. falciparum may have rapidly spread from its African tropical origins to the tropical and subtropical regions of the world only within the last 6,000 years. The recent origin of the world-wide P. falciparum populations may account for its virulence, as the most malignant of human malarial parasites.},
	keywords = {Africa, Animals, Asia, Climate, Demography, DNA, Protozoan, Evolution, Molecular, Genes, Protozoan, Humans, Life Cycle Stages, Malaria, Malaria, Falciparum, Netherlands, Phylogeny, Plasmodium, Plasmodium falciparum, Polymorphism, Genetic, South America, Tetrahydrofolate Dehydrogenase, Time},
	issn = {0027-8424},
	author = {Rich, S M and Licht, M C and Hudson, R R and Ayala, F J}
}
@article {794,
	title = {Plasmodium falciparum antigenic diversity: evidence of clonal population structure.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {94},
	year = {1997},
	month = {1997 Nov 25},
	pages = {13040-5},
	abstract = {Plasmodium falciparum, the agent of malignant malaria, is one of mankind{\textquoteright}s most severe scourges. Efforts to develop preventive vaccines or remedial drugs are handicapped by the parasite{\textquoteright}s rapid evolution of drug resistance and protective antigens. We examine 25 DNA sequences of the gene coding for the highly polymorphic antigenic circumsporozoite protein. We observe total absence of silent nucleotide variation in the two nonrepeated regions of the gene. We propose that this absence reflects a recent origin (within several thousand years) of the world populations of P. falciparum from a single individual; the amino acid polymorphisms observed in these nonrepeat regions would result from strong natural selection. Analysis of these polymorphisms indicates that: (i) the incidence of recombination events does not increase with nucleotide distance; (ii) the strength of linkage disequilibrium between nucleotides is also independent of distance; and (iii) haplotypes in the two nonrepeat regions are correlated with one another, but not with the central repeat region they span. We propose two hypotheses: (i) variation in the highly polymorphic central repeat region arises by mitotic intragenic recombination, and (ii) the population structure of P. falciparum is clonal--a state of affairs that persists in spite of the necessary stage of physiological sexuality that the parasite must sustain in the mosquito vector to complete its life cycle.},
	keywords = {Amino Acid Sequence, Animals, Antigens, Protozoan, Molecular Sequence Data, Phylogeny, Plasmodium falciparum, Polymorphism, Genetic, Protozoan Proteins, Recombination, Genetic, Sequence Homology, Amino Acid},
	issn = {0027-8424},
	author = {Rich, S M and Hudson, R R and Ayala, F J}
}
