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MBE Advance Access published online on January 22, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm013
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Genetic Diversity and Selection at the Plasmodium vivax Apical Membrane Antigen-1 (PvAMA-1) locus in a Sri Lankan population

Anusha M. Gunasekera{dagger}, Thilan Wickramarachchi{dagger},{ddagger},*, Daniel E. Neafsey{dagger},§, Ishani Ganguli, Lakshman Perera*,&, Prasad H. Premaratne{ddagger}, Daniel Hartl$, Shiroma M. Handunnetti#,*, Preethi V. Udagama-Randeniya{ddagger} and Dyann F. Wirth

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston MA, USA
{ddagger} Department of Zoology, University of Colombo, Sri Lanka
* Malaria Research Unit, University of Colombo, Sri Lanka
§ Broad Research Institute, Cambridge, MA, USA
& Health Center , University of Ruhuna , Meddawaththa , Matara , Sri Lanka
$ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, USA
# Institute of Biochemistry, Molecular Biology & Biotechnology, University of Colombo, Sri Lanka

Corresponding author: D. F. Wirth. email: dfwirth{at}hsph.harvard.edu; tel: 617-432-4629; fax: 617-432-4766

Accepted for publication January 9, 2007.

Plasmodium vivax apical membrane antigen 1 (PvAMA-1) is an important malaria vaccine candidate. We present the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Sri Lanka. In contrast to what has been observed at the AMA-1 locus of Plasmodium falciparum, the signature of diversifying selection is seen most strongly in Domain II of PvAMA-1, indicating that the different domains in each species may be subject to varying selective pressures and functional constraints. We also find that recombination plays an important role in generating haplotype diversity at this locus, even in a region of low endemicity such as Sri Lanka. Mapping of diversity and recombination hotspots onto a three-dimensional structural model of the protein indicates that one surface of the molecule may be particularly likely to bear epitopes for antibody recognition. Regions of this surface that show constrained variability may prove to be promising vaccine targets.

Key Words: selection • Plasmodium vivax • genetic diversity • recombination

{dagger} All authors (T.W., D.E.N and A.M.G) made equally significant contributions to this work


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