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Evolutionary analysis of genes of two pathways involved in placental malaria infection

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Abstract

Placental malaria is a special form of malaria that causes up to 200,000 maternal and infant deaths every year. Previous studies show that two receptor molecules, hyaluronic acid and chondroitin sulphate A, are mediating the adhesion of parasite-infected erythrocytes in the placenta of patients, which is believed to be a key step in the pathogenesis of the disease. In this study, we aimed at identifying sites of malaria-induced adaptation by scanning for signatures of natural selection in 24 genes in the complete biosynthesis pathway of these two receptor molecules. We analyzed a total of 24 Mb of publicly available polymorphism data from the International HapMap project for three human populations with European, Asian and African ancestry, with the African population from a region of presently and historically high malaria prevalence. Using the methods based on allele frequency distributions, genetic differentiation between populations, and on long-range haplotype structure, we found only limited evidence for malaria-induced genetic adaptation in this set of genes in the African population; however, we identified one candidate gene with clear evidence of selection in the Asian population. Although historical exposure to malaria in this population cannot be ruled out, we speculate that it might be caused by other pathogens, as there is growing evidence that these molecules are important receptors in a variety of host-pathogen interactions. We propose to use the present methods in a systematic way to help identify candidate regions under positive selection as a consequence of malaria.

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Acknowledgments

This study funded by Ministerio de Educación y Ciencia, Spain (SAF2007-63171 to JB, and BFU2005-00243), Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608) and the National Institute for Bioinformatics (www.inab.org), a platform of Genoma España. MS is supported by a Ph.D. fellowship from the Programa de becas FPU del Ministerio de Educación y Ciencia, Spain (AP2005-3982). We are grateful to Pedro Alonso and Clara Menéndez for fruitful discussion about the pathogenesis of placental malaria. We also would like to thank Elena Bosch, Francesc Calafell, David Comas and Arcadi Navarro for providing very useful comments on the draft version of the manuscript and Andrés Moreno for helpful discussion. We also thank four anonymous reviewers for their helpful comments.

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Authors and Affiliations

  1. Evolutionary Biology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Carrer Dr Aiguader 88, 08003, Barcelona, Catalonia, Spain

    Martin Sikora, Anna Ferrer-Admetlla, Jaume Bertranpetit & Ferran Casals

  2. Barcelona Center for International Health Research (CRESIB), Hospital Clínic, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Catalonia, Spain

    Alfredo Mayor

  3. Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique

    Alfredo Mayor

  4. CIBER en Epidemiología y Salud Pública CIBERESP, Barcelona, Spain

    Jaume Bertranpetit

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  1. Martin Sikora
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  2. Anna Ferrer-Admetlla
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  4. Jaume Bertranpetit
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  5. Ferran Casals
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Correspondence to Ferran Casals.

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Sikora, M., Ferrer-Admetlla, A., Mayor, A. et al. Evolutionary analysis of genes of two pathways involved in placental malaria infection. Hum Genet 123, 343–357 (2008). https://doi.org/10.1007/s00439-008-0483-y

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