Human Genetics

, Volume 123, Issue 4, pp 343–357

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

Authors

  • Martin Sikora
    • Evolutionary Biology Unit, Department of Experimental and Health SciencesUniversitat Pompeu Fabra
  • Anna Ferrer-Admetlla
    • Evolutionary Biology Unit, Department of Experimental and Health SciencesUniversitat Pompeu Fabra
  • Alfredo Mayor
    • Barcelona Center for International Health Research (CRESIB), Hospital Clínic, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS)Universitat de Barcelona
    • Centro de Investigação em Saúde da Manhiça (CISM)
  • Jaume Bertranpetit
    • Evolutionary Biology Unit, Department of Experimental and Health SciencesUniversitat Pompeu Fabra
    • CIBER en Epidemiología y Salud Pública CIBERESP
    • Evolutionary Biology Unit, Department of Experimental and Health SciencesUniversitat Pompeu Fabra
Original Investigation

DOI: 10.1007/s00439-008-0483-y

Cite this article as:
Sikora, M., Ferrer-Admetlla, A., Mayor, A. et al. Hum Genet (2008) 123: 343. doi:10.1007/s00439-008-0483-y

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.

Supplementary material

439_2008_483_MOESM1_ESM.doc (1.7 mb)
Supplementary information (DOC 1.67 mb)

Copyright information

© Springer-Verlag 2008