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1.
Nature ; 419(6906): 512-9, 2002 Oct 03.
Article in English | MEDLINE | ID: mdl-12368865

ABSTRACT

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.


Subject(s)
Genome, Protozoan , Plasmodium yoelii/genetics , Animals , DNA, Protozoan , Disease Models, Animal , Humans , Malaria/parasitology , Multigene Family , Plasmodium falciparum/genetics , Recombination, Genetic , Rodentia , Sequence Alignment , Sequence Analysis, DNA , Species Specificity , Synteny , Telomere
2.
Nature ; 419(6906): 531-4, 2002 Oct 03.
Article in English | MEDLINE | ID: mdl-12368868

ABSTRACT

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.


Subject(s)
DNA, Protozoan , Plasmodium falciparum/genetics , Animals , Chromosomes , Genome, Protozoan , Proteome , Protozoan Proteins/genetics , Sequence Analysis, DNA
3.
Nature ; 419(6906): 498-511, 2002 Oct 03.
Article in English | MEDLINE | ID: mdl-12368864

ABSTRACT

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.


Subject(s)
Genome, Protozoan , Plasmodium falciparum/genetics , Animals , Chromosome Structures , DNA Repair , DNA Replication , DNA, Protozoan/biosynthesis , DNA, Protozoan/genetics , Evolution, Molecular , Humans , Malaria Vaccines , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Malaria, Falciparum/prevention & control , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Molecular Sequence Data , Plasmodium falciparum/immunology , Plasmodium falciparum/metabolism , Plastids/genetics , Proteome , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/physiology , Recombination, Genetic , Sequence Analysis, DNA/methods
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