Discussion

Repetitive low complexity sequences are common in proteins that are exported by the malaria parasite into its host erythrocyte. We identify a group of exported proteins containing short lysine-rich tandemly repeated sequences that are sufficient to localise to the erythrocyte periphery where key virulence-related modifications to the plasma membrane and the underlying cytoskeleton are known to occur. Efficiency of targeting is dependent on repeat number, indicating that repeat expansion over evolutionary time can shift a protein from the erythrocyte cytoplasm to the periphery of the infected cell. Comparison of proteins from different parasite species shows that targeting sequences can evolve de novo by repeat expansion. Several proteins known to be involved in cyto-adhesion contain lysine-rich repetitive targeting sequences highlighting the importance to disease pathogenesis.