title: "Sexual" population structure and genetics of the malaria agent P. falciparum.
abstract: The population genetics and structure of P. falciparum determine the rate at which malaria evolves in response to interventions such as drugs and vaccines. This has been the source of considerable recent controversy, but here we demonstrate the organism to be essentially sexual, in an area of moderately high transmission in the Lower Shire Valley, Malawi. Seven thousand mosquitoes were collected and dissected, and genetic data were obtained on 190 oocysts from 56 infected midguts. The oocysts were genotyped at three microsatellite loci and the MSP1 locus. Selfing rate was estimated as 50% and there was significant genotypic linkage disequilibrium (LD) in the pooled oocysts. A more appropriate analysis searching for genotypic LD in outcrossed oocysts and/or haplotypic LD in the selfed oocysts found no evidence for LD, indicating that the population was effectively sexual. Inbreeding estimates at MSP1 were higher than at the microsatellites, possibly indicative of immune action against MSP1, but the effect was confounded by the probable presence of null mutations. Mating appeared to occur at random in mosquitoes and evidence regarding whether malaria clones in the same host were related (presumably through simultaneous inoculation in the same mosquito bite) was ambiguous. This is the most detailed genetic analysis yet of P. falciparum sexual stages, and shows P. falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines.
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: Themba
authors.initials: T
authors.lastname: Mzilahowa
authors.forename: Philip J
authors.initials: PJ
authors.lastname: McCall
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hastings
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D011723:Chrysanthemum cinerariifolium; D009033:Culicidae / Q000469:parasitology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006798:Housing; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D008288:Malaria / Q000453:epidemiology / Q000469:parasitology / Q000635:transmission; D008295:Malawi / Q000453:epidemiology; D018895:Microsatellite Repeats / Q000235:genetics; D033661:Oocysts / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D017931:DNA Primers; D007306:Insecticides; D004247:DNA