Genes Necessary for Expression of a Virulence Determinant and for Transmission of Plasmodium falciparum are Located on a 0.3-Megabase Region of Chromosome 9

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 17; pp. 8292 - 8296
• Main Authors: Day, K. P., Karamalis, F., Thompson, J., Barnes, D. A., Peterson, C., Brown, H., Brown, G. V., Kemp, D. J.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.09.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Agglutination; Animals; Biological and medical sciences; Cell Adhesion; Cell Line; Cell lines; Chromosome Mapping; Chromosomes; Classical genetics, quantitative genetics, hybrids; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genes; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Humans; Invertebrates; Karyotyping; Life cycle. Host-agent relationship. Pathogenesis; Malaria; Malaria, Falciparum - parasitology; Medical research; Membrane Proteins - isolation & purification; Papua New Guinea; Parasites; Parasitism; Phenotype; Phenotypes; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - isolation & purification; Plasmodium falciparum - pathogenicity; Protozoa; Protozoan Proteins - isolation & purification; Virulence; Virulence - genetics; Papua New Guinea; Genetic mapping; Pathogenicity; Protozoa; Plasmodium falciparum; Genetic inheritance; Chromosome 9; Transmission; Cytogenetics; Parasite; Sporozoa; Karyotype
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.17.8292

Virulence of the human malaria parasite Plasmodium falciparum is believed to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual development (gametocytogenesis). Continuous in vitro culture of P. falciparum frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expression of these phenotypes were karyotyped by pulse-field gel electrophoresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion frequently occurs during adaptation of parasite isolates to in vitro culture. Parasites with this deletion did not express the variant surface agglutination phenotype and the putative asexual cytoadherence ligand designated P. falciparum erythrocyte membrane protein 1, which has recently been shown to undergo antigenic variation. The syntenic relationship between asexual cytoadherence and gametocytogenesis suggests that expression of these phenotypes is genetically linked. One explanation for this linkage is that both developmental pathways share a common cytoadherence mechanism. This proposed biological and genetic linkage between a virulence factor (asexual cytoadherence) and transmissibility (gametocytogenesis) would help explain why a high degree of virulence has evolved and been maintained in falciparum malaria.