PLASMODIUM-FALCIPARUM ANTIGENIC DIVERSITY - EVIDENCE OF CLONAL POPULATION-STRUCTURE

Plasmodium falciparum, the agent of malignant malaria, is one of manki nd's most severe scourges. Efforts to develop preventive vaccines or r emedial drugs are handicapped by the parasite's rapid evolution of dru g resistance and protective antigens, We examine 25 DNA sequences of t he gene coding for the highly poly-morphic antigenic circumsporozoite protein. We observe total absence of silent nucleotide variation in th e two nonrepeated regions of the gene. We propose that this absence re flects a recent origin (within several thousand Sears) of the world po pulations of P. falciparum from a single individual; the amino acid po lymorphisms observed in these nonrepeat regions would result from stro ng natural selection, Analysis of these polymorphisms indicates that: (i) the incidence of recombination events does not increase with nucle otide distance; (ii) the strength of linkage disequilibrium between nu cleotides is also independent of distance; and (iii) haplotypes in the two nonrepeat regions are correlated with one another, but not with t he central repeat region they span. me propose two hypotheses: (i) var iation in the highly polymorphic central repeat region arises by mitot ic intragenic recombination, and (ii) the population structure of P. f alciparum is clonal-a state of affairs that persists in spite of the n ecessary stage of physiological sexuality that the parasite must susta in in the mosquito vector to complete its life cycle.