Plasmodium yoelii nigeriensis circumsporozoite gene structure and its implications for the evolution of the repeat regions

Abstract

The circumsporozoite (CS) gene encodes the most immunogenic component of the plasmodial sporozoites. The immunodominant epitope-encoding domain of the CS gene shows sequences that are repeated in tandem. A detailed analysis of the CS repeats of certain closely related malaria parasites (strains of Plasmodium cynomolgi, Plasmodium knowlesi, and Plasmodium vivax) showed that they evolve rapidly yet are well conserved within the gene. We were interested in studying whether the CS repeats of Plasmodia more distantly related to these species evolve in a similar manner. To this end, we isolated and characterized the Plasmodium yoelii nigeriensis CS gene. A comparative analysis of its sequence with that Plasmodium yoelii yoelii shows that both have three sets of repeats, termed PR, R1, and R2. The R1 and basically also the R2 sequences show the features observed in most CS repeats, i.e., they evolve rapidly and are nearly perfectly tandemly repeated. In contrast, the PR repeats are not internally conserved nor divergent in sequence. The implications of these findings for the evolution of the CS repeats are discussed.