The human malaria parasite Plasmodium faiciparum evades host immunity by varying the antigenic and adhesive character of infected erythrocytes. We describe a large and extremely diverse family of P. faiciparum genes (var) that encode 200-350 kDa proteins having the expected properties of antigenicaiiy variant adhesion molecules. Predicted amino acid sequences of Yar genes show a variable extraceiluiar segment with domains having receptor-binding features, a transmembrane sequence, and a terminal segment that is a probable submembrane anchor. There are 50-150 Yar genes on multiple parasite chromosomes, and some are in clustered arrangements. yar probes detect two classes of transcripts in steady-state RNA: 7-9 kb yaf transcripts, and an unusual family of 1.8-2.4 kb transcripts that may be involved in expression or rearrangements of var genes. introduction

Antigenic variation, defined as changes in exposed antigenie determinants at frequencies much higher than the underlying mutation r&e, is one of the major means by which bacteria and protozoa can maintain persistent infection in the presence of continual immune attack (Bloom, 1979). Well-known examples are the variations in the pilins and P. Ii proteins of Neisseria gonorrhoeae, the variations in the major proteins of Borrelia hermsii, and the switches of variant-specific surface glycoproteins of the African trypanosomes (reviewed by Borst and Greaves, 1987; Seifert and So, 1988). in these organisms, antigenic switching occurs principally by DNA rearrangements that move gene sequences from large repertoires of silent copies into active expression sites. The expression sites may themselves also change and may be associated with recombination events that generate novel antigenic forms. As a result, the organisms are capable of producing vast serotype diversity that enables them to deflect immune recognition and maintain infection. Malaria is a persistent disease caused by Plasmodium