Allele frequency-based analyses robustly map sequence sites under balancing selection in a malaria vaccine candidate antigen.
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.
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. spencer.polley@lshtm.ac.uk
Spencer D
SD
Polley
Watcharee
W
Chokejindachai
David J
DJ
Conway
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D015810:Linkage Disequilibrium; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium