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Proc Natl Acad Sci U S A. Oct 15, 1996; 93(21): 11889–11894.

Comparison of circumsporozoite proteins from avian and mammalian malarias: biological and phylogenetic implications.


The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species.

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  • Dame JB, Williams JL, McCutchan TF, Weber JL, Wirtz RA, Hockmeyer WT, Maloy WL, Haynes JD, Schneider I, Roberts D, et al. Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science. 1984 Aug 10;225(4662):593–599. [PubMed]
  • Adams JH, Sim BK, Dolan SA, Fang X, Kaslow DC, Miller LH. A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7085–7089. [PMC free article] [PubMed]
  • Cerami C, Frevert U, Sinnis P, Takacs B, Clavijo P, Santos MJ, Nussenzweig V. The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites. Cell. 1992 Sep 18;70(6):1021–1033. [PubMed]
  • Aley SB, Bates MD, Tam JP, Hollingdale MR. Synthetic peptides from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium knowlesi recognize the human hepatoma cell line HepG2-A16 in vitro. J Exp Med. 1986 Dec 1;164(6):1915–1922. [PMC free article] [PubMed]
  • Chitnis CE, Miller LH. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J Exp Med. 1994 Aug 1;180(2):497–506. [PMC free article] [PubMed]
  • Sim BK, Chitnis CE, Wasniowska K, Hadley TJ, Miller LH. Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science. 1994 Jun 24;264(5167):1941–1944. [PubMed]
  • Dame JB, McCutchan TF. Plasmodium falciparum: Hoechst dye 33258-CsCl ultracentrifugation for separating parasite and host DNAs. Exp Parasitol. 1987 Oct;64(2):264–266. [PubMed]
  • Krettli AU, Rocha EM, Lopes JD, Carneiro CR, Kamboj KK, Cochrane AH, Nussenzweig RS. Circumsporozoite protein of Plasmodium gallinaceum characterized by monoclonal antibodies. Parasite Immunol. 1988 Sep;10(5):523–533. [PubMed]
  • McCutchan TF, Hansen JL, Dame JB, Mullins JA. Mung bean nuclease cleaves Plasmodium genomic DNA at sites before and after genes. Science. 1984 Aug 10;225(4662):625–628. [PubMed]
  • Higgins DG, Sharp PM. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. [PubMed]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • Ramirez AD, Rocha EM, Krettli AU. Antisporozoite antibodies with protective and nonprotective activities: in vitro and in vivo correlations using Plasmodium gallinaceum, an avian model. J Eukaryot Microbiol. 1995 Nov-Dec;42(6):705–708. [PubMed]
  • Galinski MR, Arnot DE, Cochrane AH, Barnwell JW, Nussenzweig RS, Enea V. The circumsporozoite gene of the Plasmodium cynomolgi complex. Cell. 1987 Jan 30;48(2):311–319. [PubMed]
  • Sinnis P, Clavijo P, Fenyö D, Chait BT, Cerami C, Nussenzweig V. Structural and functional properties of region II-plus of the malaria circumsporozoite protein. J Exp Med. 1994 Jul 1;180(1):297–306. [PMC free article] [PubMed]
  • Goundis D, Reid KB. Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs. Nature. 1988 Sep 1;335(6185):82–85. [PubMed]
  • Robson KJ, Hall JR, Jennings MW, Harris TJ, Marsh K, Newbold CI, Tate VE, Weatherall DJ. A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature. 1988 Sep 1;335(6185):79–82. [PubMed]
  • Rich KA, George FW, 4th, Law JL, Martin WJ. Cell-adhesive motif in region II of malarial circumsporozoite protein. Science. 1990 Sep 28;249(4976):1574–1577. [PubMed]
  • Escalante AA, Barrio E, Ayala FJ. Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene. Mol Biol Evol. 1995 Jul;12(4):616–626. [PubMed]
  • 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]
  • Arnot DE, Barnwell JW, Stewart MJ. Does biased gene conversion influence polymorphism in the circumsporozoite protein-encoding gene of Plasmodium vivax? Proc Natl Acad Sci U S A. 1988 Nov;85(21):8102–8106. [PMC free article] [PubMed]
  • Ramirez AD, Rocha EM, Krettli AU. In vitro development of exoerythrocytic forms of Plasmodium gallinaceum sporozoites in avian macrophages. J Protozool. 1991 Jan-Feb;38(1):40–44. [PubMed]
  • Sinden RE, Canning EU, Bray RS, Smalley ME. Gametocyte and gamete development in Plasmodium falciparum. Proc R Soc Lond B Biol Sci. 1978 Jun 5;201(1145):375–399. [PubMed]
  • McCutchan TF, Dame JB, Miller LH, Barnwell J. Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science. 1984 Aug 24;225(4664):808–811. [PubMed]
  • Brooks DR, McLennan DA. The evolutionary origin of Plasmodium falciparum. J Parasitol. 1992 Jun;78(3):564–566. [PubMed]
  • Ayala FJ, Fitch WM. Phylogeny of plasmodium falciparum. Parasitol Today. 1992 Mar;8(3):74–75. [PubMed]
  • Siddall ME, Barta JR. Phylogeny of Plasmodium species: estimation and inference. J Parasitol. 1992 Jun;78(3):567–568. [PubMed]
  • Corredor V, Enea V. Plasmodial ribosomal RNA as phylogenetic probe: a cautionary note. Mol Biol Evol. 1993 Jul;10(4):924–926. [PubMed]
  • Escalante AA, Ayala FJ. Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11373–11377. [PMC free article] [PubMed]
  • McCutchan TF, Li J, McConkey GA, Rogers MJ, Waters AP. The cytoplasmic ribosomal RNAs of Plasmodium spp. Parasitol Today. 1995 Apr;11(4):134–138. [PubMed]
  • Miller LH, Mason SJ, Dvorak JA, McGinniss MH, Rothman IK. Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science. 1975 Aug 15;189(4202):561–563. [PubMed]

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