title: Comparison of genomic signatures of selection on Plasmodium falciparum between different regions of a country with high malaria endemicity.
abstract: BACKGROUND
  Genome 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.
  
  
  RESULTS
  High 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.
  
  
  CONCLUSIONS
  Against 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.
authors.affiliation: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. craig.duffy@lshtm.ac.uk.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Duffy
authors.affiliation: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. samuel.assefa@lshtm.ac.uk.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Assefa
authors.affiliation: West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Box LG 54, Volta Road, Legon, Accra, Ghana. jmsabugri@gmail.com.|Department of Applied Chemistry and Biochemistry, University for Development Studies, Tamale, Ghana. jmsabugri@gmail.com.
authors.forename: James
authors.initials: J
authors.lastname: Abugri
authors.affiliation: Kintampo Health Research Centre, Kintampo, Ghana. nicholas.amoako@kintampo-hrc.org.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Amoako
authors.affiliation: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. seth.owusu-agyei@lshtm.ac.uk.|Kintampo Health Research Centre, Kintampo, Ghana. seth.owusu-agyei@lshtm.ac.uk.
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
authors.affiliation: Navrongo Health Research Centre, Navrongo, Ghana. tanyorigiya@navrongo.mimcom.org.
authors.forename: Thomas
authors.initials: T
authors.lastname: Anyorigiya
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. bronwyn@broadinstitute.org.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: MacInnis
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. dominic@well.ox.ac.uk.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. dominic@well.ox.ac.uk.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.affiliation: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. david.conway@lshtm.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
authors.affiliation: West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Box LG 54, Volta Road, Legon, Accra, Ghana. gawandare@ug.edu.gh.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Awandare
mesh_terms: D055028:Comparative Genomic Hybridization; D005787:Gene Frequency; D049751:Genome, Helminth; D005838:Genotype; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA