Hypothetical model of var gene evolution Hypothetical model of var gene evolution. var genes are confined to human malaria (P. falciparum) and chimpanzee malaria (P. reichenowi) and appear to have evolved in the common progenitor to these organisms, presumably after acquiring the DBL adhesion domain from erythrocyte invasion ligands found in diverse Plasmodium species (1). Hypothetical model of var gene evolution. var genes are confined to human malaria (P. falciparum) and chimpanzee malaria (P. reichenowi) and appear to have evolved in the common progenitor to these organisms, presumably after acquiring the DBL adhesion domain from erythrocyte invasion ligands found in diverse Plasmodium species (1). An original ancestral var gene may have evolved by gene duplication, gene inversion (A and B var groups), and gene diversification into the present var groupings. The three main var groups (A, B, and C) are found in parasite isolates from Africa, Southeast Asia, and Central America, indicating this division predates the continental separation of P. falciparum isolates. The presence of A, B, and C var groups in P. reichenowi has not yet been established. The variant antigen repertoire also contains three unusual strain-transcendent var genes (var1CSA, var2CSA, and type 3 var genes). While var1CSA and var2CSA have ancient origins, a type 3 var gene has not been identified in P. reichenowi. However, there is only one partially sequenced P. reichenowi isolate, and it is possible the gene may have been deleted from the reference isolate. Sue A. Kyes et al. Eukaryotic Cell 2007; doi:10.1128/EC.00173-07