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

Abstract

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 (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 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.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

“…The trend towards a negative correlation between levels of genetic diversity and malaria transmission contrasts with the pattern observed for P. falciparum , for which highest diversity is seen in high-transmission settings [8,15]. This contrast is surprising and may reflect differences in the demographic history and biology of these major human parasites.…”

“…Parasite populations clustered according to their continental origins, with most variation found within locations in highly endemic areas. Nevertheless, substantial divergence was seen between subpopulations in South America [8]. Putatively neutral microsatellite markers, sampled from across the genome [9], have recently been used to characterize field populations of P. vivax [10-12], suggesting that a spectrum of population structures also exists for this species.…”

Evolutionary structure of Plasmodium falciparum major variant surface antigen genes in South America: Implications for epidemic transmission and surveillance

“…Like the neutral/non‐selected markers, var DBLα type structuring was also consistent with an isolation‐by‐distance model. The significant genetic differentiation obtained could be explained by the “limited” genetic diversity observed in the populations under study (Hedrick, 2005), the epidemic characteristic and small effective size of South American P. falciparum populations (Anderson et al., 2000) as well as multiple independent introductions of P. falciparum into South America (Yalcindag et al., 2012). …”

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

“…Stutter peaks result from DNA strand slippage during PCR at intervals corresponding to nucleotide repeat sizes (de Valk et al 2007). A minimum value of either one-third (Anderson et al 2000, Imwong et al 2007a, Karunaweera et al 2008 or one-fourth (Anderson et al 1999) of the predominant allele peak height has been used as a cut-off to differentiate minor alleles from stutter or unspecific peaks, but the sensitivity and specificity of these criteria remain undetermined (Greenhouse et al 2006, Havryliuk et al 2008.…”