Circumsporozoite Protein Genes of Malaria Parasites (Plasmodium Spp.): Evidence for Positive Selection on Immunogenic Regions
AUTOR(ES)
Hughes, A. L.
RESUMO
The circumsporozoite (CS) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (Plasmodium spp.) that infects the vertebrate host. Analysis of DNA sequences supports the hypothesis that in Plasmodium falciparum, positive Darwinian selection favors diversity in the T-cell epitopes (peptides presented to T cells by host MHC molecules) of the CS protein. In gene regions encoding T cell epitopes of P. falciparum, the rate of nonsynonymous nucleotide substitution is significantly higher than that of synonymous substitution, whereas this is not true of other gene regions. Furthermore nonsynonymous nucleotide substitutions in these regions cause a change of amino acid residue charge significantly more frequently than expected by chance. By contrast, in Plasmodium cynomolgi, the same regions show no evidence of positive selection, and residue charge is conserved. The CS protein has a central repeat region, which is the target of host antibodies. In P. falciparum, the amino acid sequence of the repeat region is conserved within and between alleles. In P. cynomolgi, on the other hand, there is evidence that positive selection has favored evolution of two different repeat types within a given allele.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1204362Documentos Relacionados
- Antibody-mediated elimination of malaria parasites (plasmodium berghei) in vivo.
- Calcium and calmodulin antagonists inhibit human malaria parasites (Plasmodium falciparum): implications for drug design.
- Initial extracellular development in vitro of erythrocytic stages of malaria parasites (Plasmodium falciparum).
- Demonstration of the role of cytophilic antibody in resistance to malaria parasites (Plasmodium berghei) in rats.
- Human T lymphocyte clones specific for malaria (Plasmodium falciparum) antigens.