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Molecular Biology and Evolution 17:1467-1482 (2000)
© 2000 Society for Molecular Biology and Evolution


ARTICLE

Microsatellite Markers Reveal a Spectrum of Population Structures in the Malaria Parasite Plasmodium falciparum

Timothy J. C. Anderson2,*{dagger}, Bernhard Haubold{ddagger}, Jeff T. Williams{dagger}, Jose G. Estrada-Franco§, Lynne Richardson*, Rene Mollinedo||, Moses Bockarie, John Mokili**, Sungano Mharakurwa*, Neil French{dagger}{dagger}, Jim Whitworth{ddagger}{ddagger}, Ivan D. Velez§§, Alan H. Brockman||||, Francois Nosten||||, Marcelo U. Ferreira¶¶ and Karen P. Day*

*Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, Oxford, England;
{dagger}Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas;
{ddagger}Max-Planck-Institut fuer Chemische Oekologie, Jena, Germany;
§Center for Agricultural Biotechnology and Department of Entomology, University of Maryland College Park;
||National Malaria Program, Ministry of Health, La Paz, Bolivia;
¶Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea;
**HIV Research Program, Henry M. Jackson Foundation, Rockville, Maryland;
{dagger}{dagger}Liverpool School of Tropical Medicine, Liverpool, England;
{ddagger}{ddagger}Medical Research Council Research Programme on AIDS in Uganda Uganda Virus Research Institute, Entebbe, Uganda;
§§Programa de Estudio y Control de Enfermedades Tropicales, Universidad de Antioquia, Medellin, Colombia;
||||Shoklo Malaria Research Unit, Mae Sot Tak, Thailand;
¶¶Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also 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 (FST = 0.364) and within locations in Africa (FST = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting 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 structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.


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