FIGURE 4. Partial alignment of MspI (block 8) group I and II alleles. Alternating odd and even occurrence of a repeat is indicated by underline and overbar, respectively. Region R2a consists of five tandem repeats of a 9-bp sequence (agaaacaga, in italics) highlighted in the five group II alleles (Upper); one copy is missing in the RO33 allele. Regions R1a and R1b consist of two repeats, measuring 7-bp (acaagca, in boldface; repeated five times) and 6-bp (accagt, shown in inverted text; repeated four times) found in group I alleles. The five 7-bp repeats (except for two) are separated by several codons, whereas the 6-bp repeats occur in tandem. There are no repeat sequences shared between groups I and II; however, the 6-bp repeat in group I alleles clearly derives from a deletion of the intervening lightly shaded portion of group II alleles, followed by duplication of the resulting accagt motif (junction indicated by arrows). In this regard, the Camp, Palo Alto-1, and RO33 alleles are intermediate between MAD20/3D7 and K1/ Palo Alto-2/Wellcome alleles.
sequence; but the distribution of these nucleotide repeats is not likely to differ markedly between chromosomes by chance alone.
We have made two interesting observations while searching chromosome 2 and 3 sequences for the presence of these nucleotide repeats. First, five of the 11 R2a repeats found on chromosome 2 are located within a 558-bp region corresponding to a predicted secreted antigen that appears similar to the glutamic acid-rich protein gene. Second, 67 of the 116 R1a nucleotide repeats on chromosome 2 occur as the 3 ′ terminus of a 39-nt repeat within the pfEMP member of the var gene family, which is an important component of P. falciparum antigenic variation. The observation of highly significant repeats within regions of the Msp-1 gene previously thought not to be repetitive makes it clear that the extensive between-group nucleotide diversity between the two allelic groups is attributable to the same kinds of repeat variation and rapid divergence known in other antigenic determinants.