title: 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 FSTscan 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.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Duffy
authors.affiliation: Institut National de Recherche en Sante Publique, Nouakchott, Mauritania.
authors.forename: Hampate
authors.initials: H
authors.lastname: Ba
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Assefa
authors.affiliation: Laboratory of Bacteriology and Virology, Le Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Ambroise D
authors.initials: AD
authors.lastname: Ahouidi
authors.affiliation: Institut National de Recherche en Sante Publique, Nouakchott, Mauritania.
authors.forename: Yacine B
authors.initials: YB
authors.lastname: Deh
authors.affiliation: Institut National de Recherche en Sante Publique, Nouakchott, Mauritania.
authors.forename: Abderahmane
authors.initials: A
authors.lastname: Tandia
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
authors.forename: Freja C M
authors.initials: FCM
authors.lastname: Kirsebom
authors.affiliation: Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
authors.forename: David J
authors.identifier: http://orcid.org/0000-0002-8711-3037
authors.initials: DJ
authors.lastname: Conway
mesh_terms: D000352:Africa, Northern; D000354:Africa, Western; D000818:Animals; D051456:Gene Flow; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D018895:Microsatellite Repeats; D010963:Plasmodium falciparum / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
keywords: adaptation; biomedicine; disease biology; ecological genetics; genomics/proteomics; microbial biology