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

Abstract

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 ofPlasmodium 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. gaUinaceum most closely related to the human malaria Plasmodium fakciparum. 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. gaUlinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region 1I-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.Comparisons of homologous proteins from distantly related Plasmodium species have suggested domains retained for function. Two examples are conserved regions of the circumsporozoite (CS) protein of sporozoites (1) and the conserved regions of a family of erythrocyte binding proteins on merozoites (2). Sporozoites are the infective form of malaria parasites that are inoculated by mosquitoes into the vertebrate host. The merozoite is the parasite stage that invades erythrocytes. A comparison of CS protein sequences from Plasmodium falciparum and the distantly related parasites, Plasmodium knowlesi and Plasmodium vivax, identified domains (regions I and II) that were shown to be conserved (1) and there is evidence suggesting that these domains function in sporozoite binding to hepatocytes (3,4). A similar approach identified domains on a family of merozoite proteins that were demonstrated to bind erythrocytes (5, 6).Although the processes whereby the sporozoite develops and infects the invertebrate and vertebrate hosts are similar among Plasmodium species, there are a few fundamental differences (7). For example, sporozoites of avian malaria parasites develop predominantly in culicine mosquitoes, while the primate malarias use a...

Evolution of human-chimpanzee differences in malaria susceptibility: Relationship to human genetic loss of N -glycolylneuraminic acid

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Anopheles stephensi salivary glands bear receptors for region I of the circumsporozoite protein of Plasmodium falciparum

“…A comparison of the residues upstream of region I reveals that although this region is not conserved, it always contains a cluster of basic residues with 2 or 3 acidic residues (Table 2). Further studies will hopefully elucidate whether differences in this region of CS among different Plasmodium species are responsible for some of the species specificity between the parasite and its mosquito host [18,19].…”

A monkey's tale: The origin of Plasmodium vivax as a human malaria parasite

“…Initial phylogenetic investigations using molecular approaches have focused primarily on the origin of Plasmodium falciparum, the agent of malignant tertian malaria, and its relationship to other human and animal malaria parasite species (2)(3)(4)(5)(6)(7)(8). Two major conclusions were drawn from these studies.…”