1. Long- and Short-Term Selective Forces on Malaria Parasite Genomes
- Author
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Thomas D. Otto, Anders Krogh, Daniel C. Jeffares, Stijn van Dongen, Paul P. Gardner, Matthew Berriman, Sanne Nygaard, Gareth Malsen, Arnab Pain, Jon McAuliffe, Emmanouil T. Dermitzakis, and Alexander Braunstein
- Subjects
Plasmodium ,Cancer Research ,Time Factors ,Genes, Protozoan ,Selection, Genetic ,Genome ,Open Reading Frames/genetics ,Genome, Protozoan/*genetics ,Negative selection ,ddc:576.5 ,Evolutionary Biology/Genomics ,Conserved Sequence ,Phylogeny ,Genetics (clinical) ,Genetics ,0303 health sciences ,Natural selection ,030302 biochemistry & molecular biology ,3. Good health ,Infectious Diseases ,Conserved Sequence/genetics ,Genetics and Genomics/Comparative Genomics ,Plasmodium yoelii ,Research Article ,lcsh:QH426-470 ,Bacterial genome size ,Genes, Protozoan/genetics ,Biology ,Parasites/*genetics ,Open Reading Frames ,03 medical and health sciences ,Species Specificity ,Phylogenetics ,Genetics and Genomics/Population Genetics ,parasitic diseases ,Genetic model ,Malaria/*parasitology ,Animals ,Parasites ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Plasmodium/*genetics ,030304 developmental biology ,Plasmodium falciparum ,biology.organism_classification ,Malaria ,lcsh:Genetics ,Evolutionary biology ,Genome, Protozoan - Abstract
Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ∼23 Mb genomes encoding ∼5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes have a significant impact on malaria control, the selective pressures within Plasmodium genomes are poorly understood, particularly in the non-protein-coding portion of the genome. We use evolutionary methods to describe selective processes in both the coding and non-coding regions of these genomes. Based on genome alignments of seven Plasmodium species, we show that protein-coding, intergenic and intronic regions are all subject to purifying selection and we identify 670 conserved non-genic elements. We then use genome-wide polymorphism data from P. falciparum to describe short-term selective processes in this species and identify some candidate genes for balancing (diversifying) selection. Our analyses suggest that there are many functional elements in the non-genic regions of these genomes and that adaptive evolution has occurred more frequently in the protein-coding regions of the genome., Author Summary Malaria causes debilitating ill-health in millions of people and kills about one million people annually, mostly young children. It is caused by a single-cell Plasmodium parasite transmitted to humans via mosquito bites. It is difficult to control this parasite because variable genetic make-up enables it to evade detection by vaccines and because drug resistance has repeatedly evolved. Therefore any progress in our understanding of the evolution and genetic variation of the parasite will be central to controlling the parasite. Genic regions that encode proteins are comparatively easy to characterize, whereas non-genic regions are poorly understood. We compare the genomes of seven distantly-related Plasmodium species and find that some of the non-genic regions are very similar between species. The absence of significant evolutionary differences between these non-genic regions implies that they play an important role in the survival of the organism. We then compare the genomes of thirteen different strains of Plasmodium falciparum. It is currently accepted that several families of antigenic parasite genes evolve rapidly. However, using two methods we demonstrate that many other genes have also undergone adaptive evolution.
- Published
- 2010
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