Journal article

Hypervariable antigen genes in malaria have ancient roots

Martine M Zilversmit, Ella K Chase, Donald S Chen, Philip Awadalla, Karen P Day, Gil McVean



BACKGROUND: The var genes of the human malaria parasite Plasmodium falciparum are highly polymorphic loci coding for the erythrocyte membrane proteins 1 (PfEMP1), which are responsible for the cytoaherence of P. falciparum infected red blood cells to the human vasculature. Cytoadhesion, coupled with differential expression of var genes, contributes to virulence and allows the parasite to establish chronic infections by evading detection from the host's immune system. Although studying genetic diversity is a major focus of recent work on the var genes, little is known about the gene family's origin and evolutionary history. RESULTS: Using a novel hidden Markov model-based approach and var seq..

View full abstract

University of Melbourne Researchers


Awarded by National Institutes of Health Ruth L. Kirschstein National Research Service Award

Awarded by Wellcome Trust Program Grant Award

Awarded by NIH NIAID

Funding Acknowledgements

The work in this paper would not be possible without the free availability of unpublished data from the Wellcome Trust Sanger Institute. Additionally, we would like to thank Dr. Sue Kyes for access to HB3 var gene sequences, to Dr. James Cotton for helpful discussion on the var gene DBL alpha phylogeny, Dr. Jane Carlton for helpful discussion on gene family evolution, to Dr. Sebastian Gurevich for aid in manuscript preparation, and two anonymous reviewers for helpful comments. This work was supported by a Royal Society North American Visiting Scholar Fellowship (MMZ and GM), a National Institutes of Health Ruth L. Kirschstein National Research Service Award (F32AI071765, DSC), an EPSRC studentship (EKC), a Human Frontiers in Science Research Grant (PA and GM) and a Wellcome Trust Program Grant Award WT041354 (KD) to and NIH NIAID 1R01AI084156 (KD and DSC).