• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 1, 1993; 90(17): 8292–8296.
PMCID: PMC47335

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.

Abstract

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Waters AP, Higgins DG, McCutchan TF. Plasmodium falciparum appears to have arisen as a result of lateral transfer between avian and human hosts. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3140–3144. [PMC free article] [PubMed]
  • Anderson RM, May RM. Coevolution of hosts and parasites. Parasitology. 1982 Oct;85(Pt 2):411–426. [PubMed]
  • Levin BR, Svanborg Edén C. Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion. Parasitology. 1990;100 (Suppl):S103–S115. [PubMed]
  • Langreth SG, Peterson E. Pathogenicity, stability, and immunogenicity of a knobless clone of Plasmodium falciparum in Colombian owl monkeys. Infect Immun. 1985 Mar;47(3):760–766. [PMC free article] [PubMed]
  • Berendt AR, Simmons DL, Tansey J, Newbold CI, Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature. 1989 Sep 7;341(6237):57–59. [PubMed]
  • Ockenhouse CF, Ho M, Tandon NN, Van Seventer GA, Shaw S, White NJ, Jamieson GA, Chulay JD, Webster HK. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991 Jul;164(1):163–169. [PubMed]
  • Udeinya IJ, Graves PM, Carter R, Aikawa M, Miller LH. Plasmodium falciparum: effect of time in continuous culture on binding to human endothelial cells and amelanotic melanoma cells. Exp Parasitol. 1983 Oct;56(2):207–214. [PubMed]
  • Alano P, Carter R. Sexual differentiation in malaria parasites. Annu Rev Microbiol. 1990;44:429–449. [PubMed]
  • Corcoran LM, Forsyth KP, Bianco AE, Brown GV, Kemp DJ. Chromosome size polymorphisms in Plasmodium falciparum can involve deletions and are frequent in natural parasite populations. Cell. 1986 Jan 17;44(1):87–95. [PubMed]
  • Pologe LG, Ravetch JV. A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype. Nature. 322(6078):474–477. [PubMed]
  • Kemp DJ, Thompson JK, Walliker D, Corcoran LM. Molecular karyotype of Plasmodium falciparum: conserved linkage groups and expendable histidine-rich protein genes. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7672–7676. [PMC free article] [PubMed]
  • Patarapotikul J, Langsley G. Chromosome size polymorphism in Plasmodium falciparum can involve deletions of the subtelomeric pPFrep20 sequence. Nucleic Acids Res. 1988 May 25;16(10):4331–4340. [PMC free article] [PubMed]
  • Biggs BA, Kemp DJ, Brown GV. Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2428–2432. [PMC free article] [PubMed]
  • Ravetch JV. Chromosomal polymorphisms and gene expression in Plasmodium falciparum. Exp Parasitol. 1989 Jan;68(1):121–125. [PubMed]
  • Udomsangpetch R, Aikawa M, Berzins K, Wahlgren M, Perlmann P. Cytoadherence of knobless Plasmodium falciparum-infected erythrocytes and its inhibition by a human monoclonal antibody. Nature. 1989 Apr 27;338(6218):763–765. [PubMed]
  • Biggs BA, Goozé L, Wycherley K, Wilkinson D, Boyd AW, Forsyth KP, Edelman L, Brown GV, Leech JH. Knob-independent cytoadherence of Plasmodium falciparum to the leukocyte differentiation antigen CD36. J Exp Med. 1990 Jun 1;171(6):1883–1892. [PMC free article] [PubMed]
  • Forsyth KP, Philip G, Smith T, Kum E, Southwell B, Brown GV. Diversity of antigens expressed on the surface of erythrocytes infected with mature Plasmodium falciparum parasites in Papua New Guinea. Am J Trop Med Hyg. 1989 Sep;41(3):259–265. [PubMed]
  • Shirley MW, Biggs BA, Forsyth KP, Brown HJ, Thompson JK, Brown GV, Kemp DJ. Chromosome 9 from independent clones and isolates of Plasmodium falciparum undergoes subtelomeric deletions with similar breakpoints in vitro. Mol Biochem Parasitol. 1990 Apr;40(1):137–145. [PubMed]
  • Biggs BA, Culvenor JG, Ng JS, Kemp DJ, Brown GV. Plasmodium falciparum: cytoadherence of a knobless clone. Exp Parasitol. 1989 Aug;69(2):189–197. [PubMed]
  • Ockenhouse CF, Tandon NN, Magowan C, Jamieson GA, Chulay JD. Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science. 1989 Mar 17;243(4897):1469–1471. [PubMed]
  • Oquendo P, Hundt E, Lawler J, Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989 Jul 14;58(1):95–101. [PubMed]
  • Roberts DD, Sherwood JA, Spitalnik SL, Panton LJ, Howard RJ, Dixit VM, Frazier WA, Miller LH, Ginsburg V. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature. 1985 Nov 7;318(6041):64–66. [PubMed]
  • Marsh K, Howard RJ. Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science. 1986 Jan 10;231(4734):150–153. [PubMed]
  • Howard RJ. Malarial proteins at the membrane of Plasmodium falciparum-infected erythrocytes and their involvement in cytoadherence to endothelial cells. Prog Allergy. 1988;41:98–147. [PubMed]
  • Biggs BA, Goozé L, Wycherley K, Wollish W, Southwell B, Leech JH, Brown GV. Antigenic variation in Plasmodium falciparum. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9171–9174. [PMC free article] [PubMed]
  • Biggs BA, Anders RF, Dillon HE, Davern KM, Martin M, Petersen C, Brown GV. Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. J Immunol. 1992 Sep 15;149(6):2047–2054. [PubMed]
  • Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh K, Newbold CI. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992 Jun 25;357(6380):689–692. [PMC free article] [PubMed]
  • Borst P, Cross GA. Molecular basis for trypanosome antigenic variation. Cell. 1982 Jun;29(2):291–303. [PubMed]
  • Crandall I, Collins WE, Gysin J, Sherman IW. Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4703–4707. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...