IDENTIFICATION AND CLONING OF A LOCUS OF SERINE REPEAT ANTIGEN (SERA)-RELATED GENES FROM PLASMODIUM-VIVAX

Polymerase chain reaction (PCR) primers based on the cysteine proteina se-like active site regions of the Plasmodium falciparum serine repeat antigen (SERA) were used to identify related sequences within the gen ome of P. vivax. Molecular cloning and sequence analysis of similar to 25 kb of P. vivax genomic DNA revealed a cluster of five repeated SER A-like genes (V-SERA-1-5), each encoding a cysteine proteinase-related protein. In addition to DNA sequence homology, significant similariti es in deduced intron/exon organizations were also observed. The charac teristic polyserine sequence found in SERA was not present in any of t he deduced V-SERA sequences. Instead, in this region of the five genes , considerable sequence differences were found, suggesting the potenti al for antigenic variation in the V-SERA molecules. In common with SER A, however, the codon at the position corresponding to the active site cysteine residue of active mammalian and plant cysteinyl proteinases was found to be that of a serine residue in each of the V-SERA genes. Furthermore, in four of the five genes, including the expressed V-SERA -5 gene, the codon for the active site histidine residue was changed t o that of a leucine residue. These critical differences reinforce the concept-that a biological activity other than proteolysis is likely to be the primary function of the proteins encoded by this family of gen es.