Excess Polymorphisms in Genes for Membrane Proteins in Plasmodium falciparum

The detection of single-nucleotide polymorphisms in pathogenic microorganisms has normally been carried out by trial and error. Here we show that DNA hybridization with high-density oligonucleotide arrays provides rapid and convenient detection of single-nucleotide polymorphisms in Plasmodium falciparum, despite its exceptionally high adenine-thymine (AT) content (82%). A disproportionate number of polymorphisms are found in genes encoding proteins associated with the cell membrane. These genes are targets for only 22% of the oligonucleotide probes but account for 69% of the polymorphisms. Genetic variation is also enriched in subtelomeric regions, which account for 22% of the chromosome but 76% of the polymorphisms.

[1]  A. Clark.  Population genetics: Malaria variorum , 2002, Nature.

[2]  Kateryna D. Makova,et al.  Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum , 2002, Nature.

[3]  A. Hughes,et al.  Very large long–term effective population size in the virulent human malaria parasite Plasmodium falciparum , 2001, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[4]  D. Hartl,et al.  Recent Origin of Plasmodium falciparum from a Single Progenitor , 2001, Science.

[5]  Thomas E. Wellems,et al.  Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum , 2000, Nature.

[6]  S. Kyes,et al.  Var gene diversity in Plasmodium falciparum is generated by frequent recombination events. , 2000, Molecular and biochemical parasitology.

[7]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[8]  E V Koonin,et al.  Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. , 1998, Science.

[9]  James L. Winkler,et al.  Accessing Genetic Information with High-Density DNA Arrays , 1996, Science.

[10]  S. P. Fodor,et al.  Light-generated oligonucleotide arrays for rapid DNA sequence analysis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. Corcoran,et al.  Homologous recombination within subtelomeric repeat sequences generates chromosome size polymorphisms in P. falciparum , 1988, Cell.