Abstract
BackgroundGenome wide sequence analyses of malaria parasites from widely separated areas of the world have identified contrasting population structures and signatures of selection. To compare relatively closely situated but ecologically contrasting regions within an endemic African country, population samples of Plasmodium falciparum clinical isolates were collected in Ghana from Kintampo in the central forest-savannah area, and Navrongo in a drier savannah area ~350 km to the north with more seasonally-restricted transmission. Parasite DNA was sequenced and paired-end reads mapped to the P. falciparum reference genome.ResultsHigh coverage genome wide sequence data for 85 different clinical isolates enabled analysis of 121,712 single nucleotide polymorphisms (SNPs). The local populations had similar proportions of mixed genotype infections, similar SNP allele frequency distributions, and eleven chromosomal regions had elevated integrated haplotype scores (|iHS|) in both. A between-population Rsb metric comparing extended haplotype homozygosity indicated a stronger signal within Kintampo for one of these regions (on chromosome 14) and in Navrongo for two of these regions (on chromosomes 10 and 13). At least one gene in each of these identified regions is a potential target of locally varying selection. The candidates include genes involved in parasite development in mosquitoes, members of variant-expressed multigene families, and a leading vaccine-candidate target of immunity.ConclusionsAgainst a background of very similar population structure and selection signatures in the P. falciparum populations of Ghana, three narrow genomic regions showed evidence indicating local differences in historical timing or intensity of selection. Sampling of closely situated populations across heterogeneous environments has potential to refine the mapping of important loci under temporally or spatially varying selection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1746-3) contains supplementary material, which is available to authorized users.
Highlights
Genome wide sequence analyses of malaria parasites from widely separated areas of the world have identified contrasting population structures and signatures of selection
Direct comparison between a highly endemic population in Guinea and a population with lower endemicity in The Gambia indicated another locus with alleles at highly differentiated frequencies, containing the gametocyte development gene gdv1 that is essential for parasite transmission [17]
Parasite allele frequency distributions and within-host infection diversity Illumina short read sequence data obtained from 101 of the clinical infection isolates (Additional file 1: Table S1) were mapped to the 3D7 P. falciparum reference genome sequence, enabling high quality genome-wide single nucleotide polymorphisms (SNPs) calling and analysis for 85 isolates (45 from Kintampo and 40 from Navrongo) passing the quality filtering described in the Methods (Additional file 1: Table S1)
Summary
Genome wide sequence analyses of malaria parasites from widely separated areas of the world have identified contrasting population structures and signatures of selection. Malaria is a globally important disease which exhibits major differences in local epidemiology and ecology, with great variation within Africa where most cases are caused by Plasmodium falciparum [1]. Recent genome-wide analyses of Plasmodium falciparum revealed significant global population structure [9, 10], consistent with previous microsatellite genotyping surveys that indicated substantial divergence between Southeast Asia and Africa, and slight differentiation between East and West Africa [11, 12]. More local differences between parasite populations within an endemic country in Africa have not yet been investigated by genome-wide surveys with adequate sample sizes to detect differences in selective signatures
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