COMPARISON OF CIRCUMSPOROZOITE PROTEINS FROM AVIAN AND MAMMALIAN MALARIAS - BIOLOGICAL AND PHYLOGENETIC IMPLICATIONS

The circumsporozoite (CS) protein of malaria parasites (Plasmodium) co vers the surface of sporozoites that invade hepatocytes in mammalian h osts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the correspon ding proteins, identified initially by their conservation (region I an d region II), have been implicated in binding to hepatocytes. The CS g ene from the avian parasite Plasmodium gallinaceum was characterized t o compare these functional domains to those of mammalian Plasmodium an d for the study of Plasmodium evolution. The P. gallinaceum protein ha s the characteristics of CS proteins, including a secretory signal seq uence, central repeat region, regions of charged amino acids, and an a nchor sequence. Comparison with CS signal sequences reveals four disti nct groupings, with P. gallinaceum most closely related to the human m alaria Plasmodium falciparum. The 5-amino acid sequence designated reg ion I, which is identical in all mammalian CS and implicated in hepato cyte invasion, is different in the avian protein. The P. gallinaceum r epeat region consists of 9-amino acid repeats with the consensus seque nce QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is als o 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 mala ria P. falciparum is significantly more related to avian parasites tha n to other parasites infecting mammals, although the biology of sporoz oite invasion is different between the avian and mammalian species.