Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution

Abstract

To determine whether the major human malaria parasite Plasmodium falciparum exhibits fragmented population structure or local adaptation at the northern limit of its African distribution where the dry Sahel zone meets the Sahara, samples were collected from diverse locations within Mauritania over a range of ~1000 km. Microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and Illumina paired‐end sequences were obtained to yield high coverage genomewide single nucleotide polymorphism (SNP) data for 65 clinical infection samples from four locations. Most infections contained single parasite genotypes, reflecting low rates of transmission and superinfection locally, in contrast to the situation seen in population samples from countries further south. A minority of infections shared related or identical genotypes locally, indicating some repeated transmission of parasite clones without recombination. This caused some multilocus linkage disequilibrium and local divergence, but aside from the effect of repeated genotypes there was minimal differentiation between locations. Several chromosomal regions had elevated integrated haplotype scores (|iHS|) indicating recent selection, including those containing drug resistance genes. A genomewide FST scan comparison with previous sequence data from an area in West Africa with higher infection endemicity indicates that regional gene flow prevents genetic isolation, but revealed allele frequency differentiation at three drug resistance loci and an erythrocyte invasion ligand gene. Contrast of extended haplotype signatures revealed none to be unique to Mauritania. Discrete foci of infection on the edge of the Sahara are genetically highly connected to the wider continental parasite population, and local elimination would be difficult to achieve without very substantial reduction in malaria throughout the region.

Malaria epidemiology in Kobeni department, southeastern Mauritania from 2015 to 2017

“…Kobeni is the only sentinel site in Mauritania where studies on malaria epidemiology have been conducted regularly by several research teams over the past 20 years [2,7,9,[24][25][26][27][28][29][30][31][32][33]. Kobeni is situated within the 'heart' of area of seasonal but intense malaria transmission in Mauritania.…”

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

“…28 The data have also been used to study gene deletions that cause failure of rapid diagnostic tests 29 ; to characterise genetic variation in malaria vaccine antigens 30,31 ; to screen for new vaccine candidates 32 ; to investigate specific host-parasite interactions 33,34 ; and to describe the evolutionary adaptation and diversification of local parasite populations. 7,9,12,[35][36][37][38][39][40] The Pf Community Project data also provide an important resource for developing and testing new analytical and computational methods. A key area of methods development is quantification of within-host diversity 7,[41][42][43][44][45][46] , estimation of inbreeding 7,47 , and deconvolution of mixed infections into individual strains.…”

Population Genetic Analysis of Plasmodium Falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana

“…Despite this high level of genetic diversity resulting from non-synonymous nucleotide and amino acid substitutions observed, there remained a shared gene pool between the two sites that resulted in a largely homogeneous parasite population. Over the sampled range of 784.4 km kilometers between the two sites, there was gene ow between the local populations of P. falciparum based on Pfcsp sequence analysis, with pairwise index of differentiation (Fst) being less than 0.05 [33]. Principal component analysis further con rmed the lack of population structure or genetic isolation.…”

“…Principal component analysis further con rmed the lack of population structure or genetic isolation. Previous studies have indicated that human population mixing is likely to cause gene ow of P. falciparum parasites [33,34]. Despite the ecological and epidemiological diversity between the 2 sites, human movement between the two sites is signi cant and could be accounting for Pfcsp gene ow within Country.…”