Figure 1

Conserved structures at the ends of P. falciparum chromosomes. A typical chromosome is shown at the top, highlighting the position of subtelomeric blocks (SBs) and centrally located var gene arrays that occur on only a subset of chromosomes. Three typical chromosome end structures are expanded in the lower section and are represented as clustered at the nuclear periphery [19,20]. For all chromosomes, SBs 1-3 are highly conserved in both order and sequence - the individual boxes represent telomere-associated repeat elements (TAREs) 1-6, as previously described [16] - while cross-linking mediated by SB3 (made up of the degenerate 21 base-pair repeat known as Rep20; shown in blue) has been implicated in the stabilization/formation of chromosomal clusters within the cell nucleus (gray ovals) [18]. The first transcribed var gene is typically transcribed toward the centromere in SB4 (for 22 of the 24 chromosomal ends that have a terminal var). The predominant 'type 1' var genes (colored red) are found in the positions shown. A, B and C represent var upstream sequences, upsA, upsB and upsC, respectively, that are typically found upstream of var genes in the locations shown (note that upsB is found upstream of both subtelomeric and internal var genes). The rif, stevor and var genes in SB5 have a common arrangement in some, but not all, chromosome ends. For example, the arrangement of telomere-var-rif/stevor_(n) shown at the top of the cluster in the figure is found at 10 chromosome ends, but even among this group there is variation in the arrangement and orientation of transcription of the rif and stevor genes. Hence, although chromosomal clustering within the nucleus promotes ectopic recombination and the generation of diversity in virulence genes [15,19], this is likely to be limited by the variation in the gene structure within SB5.