Structure of the FIRA gene of Plasmodium falciparum

The falciparum interspersed repeat antigen (FIRA) plays a dominant role in the human antibody response to the malaria parasite Plasmodium falciparum. We have therefore determined the complete sequence of a genomic clone encoding FIRA. The FIRA gene contains a single intervening sequence, located immediately 3' to the putative hydrophobic core of a signal sequence in the short (100 amino acids) exon 1. The second exon largely encodes blocks of 13 hexapeptide repeats based loosely on the consensus sequence Pro-Val-Thr-Thr-Gln-Glu. The first block encoded 39 hexapeptides followed by about nine blocks of 13 hexapeptides interspersed between a conserved region of 81 amino acids, which is itself repeated along the molecule. Although deletions of repeats in this and four other independent clones make the exact number of blocks uncertain, this structure is supported by genomic blotting studies. As 31 variants of the repeat have been identified so far, we suggest that this extreme repeat variability must have important implications for the host immune response.