| dc.description.abstract | The Apicomplexa represent a phylum of obligate intracellular parasites that impart significant medical, veterinary, and socioeconomic burdens worldwide. The opportunistic, AIDS-associated, pathogen Toxoplasma gondii for instance, infects about one-third of the human population causing serious, life-threatening illness and birth defects in some. The genomes of fifteen apicomplexan species ranging in size from 8.3Mb to 64.0Mb have been sequenced and reveal a significant amount of plasticity in terms of size, AT-richness, introns and gene density. In many instances, genome size variation can be explained by differential expansion of repetitive DNA acquired through varying processes: intracellular organellar DNA transfer events, and proliferation of transposable elements (TEs). TEs make up the largest and most dynamic component of many multi-cellular and unicellular eukaryotic genomes. Moreover there is a positive correlation between genome size variation and accumulation of TEs. In an effort to determine the source of genomic variation and genetic innovation in several apicomplexan parasites, we aim to explore their repetitive DNA content and the potential propagation of TEs within these organisms. We also seek to ascertain the extent of mitochondrial DNA transfer in T. gondii and in four other apicomplexans Babesia, Theileria, Neospora and Plasmodium in order to facilitate a better understanding of these insidious parasites. To this end we employed a comparative genomic approach using complementary bioinformatic tools: RepeatScout, RepeatMasker, and Blast to query and classify the repetitive DNA repertoire in these parasites. Interestingly, we find that TEs tend to be rare in the apicomplexans, with only two of the fifteen genomes harboring any identifiable mobile elements. We find that for most of the apicomplexans analyzed, the repetitive DNA is comprised of multi-gene families clustered within sub-telomeric and telomeric regions, and most of these repeats may be involved in generation of antigenic variation in these parasites. The intracellular parasitic lifestyles of these parasites may to some extent confer some protection to these organisms from the invasion of mobile elements. Concomitantly, we do find very high content of mtDNA-derived sequences within the T. gondii nuclear genome, referred to as numts. With numts occupying 1.88% of the T. gondii genome, T. gondii harbors the highest density of numts ever reported, nearly a 100 fold greater than that observed in the human genome. Comprehensive characterization of numts in T. gondii reveals that they originate from all regions of the mitochondrial genome and are distributed across all 14 chromosomes. Careful examination of numt flanking regions show structural features suggesting that integration occurs at the DNA level during the repair of double-strand breaks by non-homologous end joining. Plotting the age distribution of the numts, we show the acquisition of DNA from mitochondria by T. gondii has been a continuous and probably still ongoing process, with integration events occurring ranging from 20 million years ago to less than 1 million year ago. In contrast to the T. gondii, the pattern of numt accumulation was strikingly different for the other apicomplexan genomes we analyzed, with a twofold difference between Neospora and Toxoplasma and very few to no numts detected in Plasmodium, Theileria and Babesia. These results, combined with lack of TEs within T. gondii, suggest that numts have had a considerable impact on the evolution of this parasite. | en_US |
