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

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 different locations within Mauritania over a range of ~ 1000 kilometres. Microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and Illumina paired-end sequences were obtained to yield high coverage genome-wide 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 multi-locus linkage disequilibrium and local divergence, but apart 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 incorporating drug resistance genes. A genome-wide 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 differentiation at three drug resistance loci and an erythrocyte invasion ligandgene. Contrast of extended haplotype signatures using the Rsb index revealed none to be particular to Mauritania. Contrary to expectations, discrete foci of infection on the edge of the Sahara are genetically highly connected to the wider continental parasite population