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Allele frequency-based analyses robustly map sequence sites under balancing selection in a malaria vaccine candidate antigen.

Spencer D Polley·Watcharee Chokejindachai·David J Conway
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Abstract

The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading candidate for a malaria vaccine. Here, within-population analyses of alleles from 50 Thai P. falciparum isolates yield significant evidence for balancing selection on polymorphisms within the disulfide-bonded domains I and III of the surface accessible ectodomain of AMA1, a result very similar to that seen previously in a Nigerian population. Studying the frequency of nucleotide polymorphisms in both populations shows that the between-population component of variance (F(ST)) is significantly lower in domains I and III compared to the intervening domain II and compared to 11 unlinked microsatellite loci. A nucleotide site-by-site analysis shows that sites with exceptionally high or low F(ST) values cluster significantly into serial runs, with four runs of low values in domain I and one in domain III. These runs may map the sequences that are consistently under the strongest balancing selection from naturally acquired immune responses.

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AnimalsAntigens, ProtozoanGene FrequencyLinkage DisequilibriumMalaria VaccinesMembrane ProteinsMolecular Sequence DataPlasmodium falciparumPolymorphism, Single NucleotideProtozoan ProteinsRecombination, GeneticSelection, GeneticSequence Analysis, DNAJournal ArticleResearch Support, Non-U.S. Gov't

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Spencer D Polley, Watcharee Chokejindachai, David J Conway. 2003. Allele frequency-based analyses robustly map sequence sites under balancing selection in a malaria vaccine candidate antigen.. https://doi.org/10.1093/genetics%2F165.2.555

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