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:

PDF 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.  
 
PDF Roy, S. W., M. U. Ferreira, and D. L. Hartl. 2008. Evolution of allelic dimorphism in malarial surface antigens. Heredity 100: 103-110.  
 
PDF 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.  
 
PDF 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.  
 
PDF 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.  
 
PDF 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.