Genetic diversity of the malaria parasite Plasmodium falciparum
Among the leading causes of death in African children is cerebral malaria caused by the parasitic protozoan
Plasmodium falciparum. Endemic forms of this disease are thought to have originated in central Africa about
10,000 years ago, coincident with the innovation of slash-and-burn agriculture and the diversification of the Anopheles
gambiae complex of mosquito vectors.
Our research focuses on several features of this important organism. First, we study the genetic diversity of P.
falciparum in order to identify candidate genes whose products likely interact with the human host and may
contribute to virulence, immune evasion, or drug resistance. We have also made use of bioinformatic analysis of the
genomes and proteomes of P. falciparum and other parasite species to help identify candidate genes, and also to
discover patterns of evolution in the history of the organism. Finally, we are using site-directed mutagenesis to
investigate the empirical fitness landscape underlying resistance to certain drugs used in the treatment of malaria.
This approach will help understand and predict the evolution of drug-resistance genes.
 
Selected publications:
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Amodu, O. K., D. L. Hartl, and S. W. Roy. 2008. Patterns of polymorphism in
genomic regions flanking three highly polymorphic surface antigens in Plasmodium falciparum.
Mol. Biochem. Parasitol. 159: 1-6.
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Roy, S. W., M. U. Ferreira, and D. L. Hartl. 2008. Evolution of allelic dimorphism
in malarial surface antigens. Heredity 100: 103-110.
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Chookajorn, T., R. Dzikowski, M. Frank, F. Li, A. Z. Jiwani, D. L. Hartl,
K. W. Deitsch. 2007. Epigenetic memory at malaria virulence genes. Proc. Natl. Acad. Sci. USA
104:899-902.
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Volkman, S. K., E. Lozovsky, A. E. Barry, T. Bedford, L. Bethke, A. Myrick, K. P. Day,
D. L. Hartl, D. F. Wirth, and S. A. Sawyer. 2007. Genomic heterogeneity in the density of noncoding
single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum. Gene 387:1-6.
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DePristo, M. A., M. M. Zilversmit, and D. L. Hartl. 2006. On the abundance, amino acid
composition, and evolutionary dynamics of low-complexity regions in proteins. Gene 378:19-30.
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Neafsey, D. E., D. L. Hartl, and M. Berriman. 2005. Evolution of noncoding and
silent coding sites in the Plasmodium falciparum and Plasmodium reichenowi genomes.
Mol. Biol. Evol. 22: 1621-1626.
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