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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites
PLoS Genetics, Volume 8, No. 11, Article e1002992, Year 2012
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Description
Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ~10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now prioritized for functional study. © 2012 Amambua-Ngwa et al.
Authors & Co-Authors
Amambua-Ngwa, Alfred
Unknown Affiliation
Tetteh, Kevin Kweku Adjei
Unknown Affiliation
Manske, Heinrich Magnus
Unknown Affiliation
Gomez-Escobar, Natalia
Unknown Affiliation
Stewart, Lindsay B.
Unknown Affiliation
Deerhake, M. Elizabeth
Unknown Affiliation
Cheeseman, Ian H.
Unknown Affiliation
Newbold, Chris I.
Unknown Affiliation
Holder, Anthony A.
Unknown Affiliation
Knuepfer, Ellen
Unknown Affiliation
Janha, O.
Unknown Affiliation
Jallow, Muminatou
Unknown Affiliation
Campino, Susana G.
Unknown Affiliation
MacInnis, Bronwyn L.
Unknown Affiliation
Kwiatkowski, Dominic P.
Unknown Affiliation
Conway, David J.
Unknown Affiliation
Statistics
Citations: 152
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pgen.1002992
e-ISSN:
15537404
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Study Approach
Quantitative