“Clonal” population structure of the malaria agent Plasmodium falciparum in high-infection regions

Abstract

The population genetic structure of Plasmodium falciparum, the agent of malignant malaria, has been shown to be predominantly ''clonal'' (i.e., highly inbred) in regions of low infectivity; in highinfectivity regions, it is often thought to be panmictic, or nearly so, although there is little supporting evidence for this. The matter can be settled by investigating the parasite's genetic makeup in the midgut oocysts of the mosquito vector, where the products of meiosis can directly be observed. The developmental stages of P. falciparum are haploid, except in the oocysts of infected mosquito vectors, where two gametes fuse, diploidy occurs, and meiosis ensues. We have investigated genetic polymorphisms at seven microsatellite loci located on five chromosomes by assaying 613 oocysts in 145 mosquitoes sampled from 11 localities of Kenya, where malignant malaria is perennial and intense. There is considerable allelic variation, 16.3 ؎ 2.1 alleles per locus, and considerable inbreeding, Ϸ50% on the average. The inbreeding is caused by selfing (Ϸ25%) and nonrandom genotype distribution of oocysts among mosquito guts (35%). The observed frequency of heterozygotes is 0.43 ؎ 0.03; the expected frequency, assuming random mating, is 0.80 ؎ 0.05. Linkage disequilibrium is statistically significant for all 21 pairwise comparisons between loci, even though 19 comparisons are between loci in different chromosomes, which is consistent with strong deviation from panmixia and the consequent reproduction of genomes as clones, without recombination between gene loci. This is of considerable evolutionary significance and of epidemiological consequence, concerning the spread of multilocus drug and vaccine resistance.epidemiology ͉ evolutionary genetics ͉ parasitism ͉ population genetics

Population genetic structure of Plasmodium falciparum in the two main African vectors, Anopheles gambiae and Anopheles funestus

“…The index of discrepancy was 0.99 for both species; the variance-to-mean ratios were 17.7 and 17.6 (Table 1). These values are characteristic of the highly aggregated oocyst distributions generally observed in anopheline mosquitoes, with a high proportion of the parasites concentrated in a small fraction of hosts (19)(20)(21).…”

“…A few earlier studies considered oocysts' genetic diversity but targeted a small number of antigen-coding loci subjected to strong host immune selection (17)(18), thus giving a possibly biased view of P. falciparum population structure. Using seven presumably neutral microsatellite loci, we have recently demonstrated that P. falciparum population structure is predominantly clonal in A. gambiae from Kenya (19). We now extend this approach to parasite populations from the two major African vector species, A. gambiae s.s. and A. funestus, collected in Central (Cameroon) and East Africa (Kenya) across successive years.…”

Effective size of the hierarchically structured populations of the agent of malaria: a coalescent-based model

“…Again, the few studies that have analysed the genetic variability of oocyst infrapopulations found strong genetic differentiation between them (Razakandrainibe et al, 2005;Annan et al, 2007). Several aspects of parasite biology or of their hosts may explain the amount of genetic differentiation observed between oocyst infrapopulations.…”

“…The few studies that have analysed it within natural oocyst infrapopulations reported high positive values (Paul et al, 1995;Razakandrainibe et al, 2005;Annan et al, 2007;Mzilahowa et al, 2007), meaning that infrapopulations harboured more homozygous individuals than expected if gametes had met at random. Two main hypotheses are generally proposed to explain a positive F IS (in our model, F IM ) in oocyst infrapopulations: selffertilization and/or Wahlund effects.…”

“…For example, malaria parasites sampled within one mosquito will be more similar to each other than parasites sampled in different, geographically adjacent mosquitoes (for example, within the same house, (Razakandrainibe et al, 2005)). This result owes in part to the co-transmission during the infection events of products of clonal reproduction.…”