Evolutionary genomics of malaria parasites
The two major human malaria parasites are Plasmodium falciparum and Plasmodium vivax. Over the past ten years, we have discovered a number of species of related parasites that infect apes in Africa (ref.1). In recent years, genome sequences have been determined for thousands of strains of P. falciparum and P. vivax, as well as for smaller numbers of the various species of ape parasites. This project aims to make use of those genome sequence data to gain a greater understanding of the evolutionary origins, spread and diversification of the human parasites. The project uses computer analyses of DNA and protein sequences to examine population genetic and phylogenetic questions.
While some analyses of these genome sequences have been done already, many of these have been superficial, or have made errors. For example, we have recently corrected erroneous conclusions from others regarding the extent of inter-species gene transfer among relatives of P. falciparum (ref.2). Comparisons of genetic diversity, between the human Plasmodium species and their ape-infecting relatives have already revealed differences in the nature of that diversity (for example, see ref.3). Those results suggest that many previous analyses of adaptive evolution of malaria parasites have been based on inappropriate comparisons.
Work on the evolution of malaria parasites in the Sharp laboratory is in collaboration with Professor Beatrice Hahn (University of Pennsylvania).
Both P. falciparum and P. vivax appear to have undergone severe genetic bottlenecks before spreading around the world. This project will use genomic data to investigate the population history of each of P. falciparum and P. vivax, and attempt to elucidate the circumstances surrounding their origins. For example, how many loci show evidence that more than one allele survived the bottleneck when a gorilla parasite jumped into humans to give rise to P. falciparum? The project will also re-examine evidence of selection during the divergence of these parasites. The results of these analyses may have implications for ongoing attempts to eradicate malaria from humans.
The project involves opportunities to learn the theoretical bases of population genetics analyses, phylogenetic analyses, and the bioinformatics analyses required for interpretation of genome sequence data.
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(1) Loy DE, et al. (2017) Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. International Journal for Parasitology 47:87-97.
(2) Plenderleith LJ, et al. (2019) Ancient introgression between two ape malaria parasite species. Genome Biology and Evolution 11:3269-3274.
(3) Loy DE, et al. (2018) Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites. Proceedings of the National Academy of Sciences, U.S.A. 115:E8450-E8459.
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