Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum

Multilocus genotyping of microbial pathogens has revealed a range of popula tion structures, with some bacteria showing extensive recombination and oth ers showing almost complete clonality. The population structure of the prot ozoan parasite Plasmodium falciparum has been harder to evaluate, since mos t studies have used a limited number of antigen-encoding loci that are know n to be under strong selection. We describe length variation at 12 microsat ellite loci in 465 infections collected from 9 locations worldwide. These d ata reveal dramatic differences in parasite population structure in differe nt locations. Strong linkage disequilibrium (LD) was observed in six of nin e populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transm ission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels o f self-fertilization in populations with low levels of transmission. We als o observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0 .3-0.4) were less than half those observed in African locations (0.76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples ( 0.51-0.65). Furthermore, variation was distributed among locations in South America (F-ST = 0.364) and within locations in Africa (F-ST = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific compar isons of plants and animals with differing levels of outcrossing, suggestin g that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population stru ctures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.