Genome Evolution, Innovation and Adaptation in the Apicomplexa
Principal Investigator: Jessica Kissinger
Abstract: DESCRIPTION (provided by applicant): Diseases caused by unicellular parasitic organisms belonging to the eukaryotic phylum Apicomplexa are notoriously difficult to treat. The most prominent organisms in this phylum are Plasmodium, the causative agent of malaria, and the AIDS-related pathogens, Toxoplasma and Cryptosporidium. Current treatments for these organisms, when they exist, are threatened by the emergence of drug resistance or are of limited efficacy. The consequence is that millions of people, primarily children, die annually. New therapeutics is needed. All good therapeutic targets have one feature in common;the target molecule/pathway in the pathogen is sufficiently distinct from similar molecules/pathways in the host such that therapeutic compounds can be discriminated between. Apicomplexan parasites, like us, are eukaryotic organisms. Thus, there are fewer novel targets available for therapeutics to discriminate between. However, apicomplexan parasites have had an eventful evolutionary history involving endo-symbiosis of a red alga and numerous gene transfers from the alga and other bacteria. These evolutionary distant sources of genetic material can provide potential new therapeutic targets. The challenge is to find them. A systematic, evolutionary genomic search of the metabolic, immune evasive and host adaptive capabilities of apicomplexan pathogens is proposed. The experimental plan described here exploits the complex evolutionary history of the Apicomplexa and the increased availability of genome sequence data for numerous parasites and their human host. The origins of novel parasite capabilities and the types of innovation and adaptation to host created by the gain or loss of particular metabolic or evasive capabilities will be investigated. The molecular mechanisms underlying the remarkable genetic plasticity of apicomplexan parasites, in particular the possible role of mobile and repetitive DNA elements in these processes will be explored. Finally, this study will reveal metabolic processes that are present, absent, or strikingly different in genera of this phylum relative to their human host. Taken together, this approach should shed considerable light on the basic biology of the Apicomplexa, reveal potential new therapeutic targets and test several important assumptions about how eukaryotic genomes evolve. The results of these studies will be shared with the larger research community via publication and deposition in community databases and Bioinformatics Resource Centers.
Funding Period: ----------------2007 - ---------------2012-
more information: NIH RePORT
- DNA transposons and the evolution of eukaryotic genomesCEDRIC FESCHOTTE
Department of Biology, University of Texas, Arlington, TX 76019, USA
Annu Rev Genet 41:331-68. 2007..Finally, we highlight how the distinctive biological features of DNA transposons have contributed to shape genome architecture and led to the emergence of genetic innovations in different eukaryotic lineages...
- Consistent and contrasting properties of lineage-specific genes in the apicomplexan parasites Plasmodium and TheileriaChih Horng Kuo
Department of Genetics, University of Georgia, Athens, GA 30602, USA
BMC Evol Biol 8:108. 2008..In parasitic organisms, lineage-specific gene products are possible targets for vaccine development or therapeutics when these genes are absent from the host genome...
- The Apicomplexan whole-genome phylogeny: an analysis of incongruence among gene treesChih Horng Kuo
Department of Genetics, University of Georgia, USA
Mol Biol Evol 25:2689-98. 2008..The importance of examining multiple, unlinked genes that possess a strong phylogenetic signal cannot be overstated...
- MCScanX: a toolkit for detection and evolutionary analysis of gene synteny and collinearityYupeng Wang
Plant Genome Mapping Laboratory, Institute of Bioinformatics, Department of Plant Biology, University of Georgia, Athens, GA 30602, USA
Nucleic Acids Res 40:e49. 2012..An integrated view of various modes of gene duplication can supplement the traditional gene tree analysis in specific families. The source code and documentation of MCScanX are freely available at http://chibba.pgml.uga.edu/mcscan2/...
- Genome cartography: charting the apicomplexan genomeJessica C Kissinger
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, USA
Trends Parasitol 27:345-54. 2011....
- Applied genomics: data mining reveals species-specific malaria diagnostic targets more sensitive than 18S rRNAAllison Demas
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30602, USA
J Clin Microbiol 49:2411-8. 2011..These novel targets provide a powerful alternative molecular diagnostic method for the detection of P. falciparum and P. vivax in conventional or multiplex PCR platforms...
- Jumbled genomes: missing Apicomplexan syntenyJeremy D DeBarry
Center for Tropical and Emerging Global Diseases, University of Georgia, USA
Mol Biol Evol 28:2855-71. 2011..It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes...
- Transposable elements and factors influencing their success in eukaryotesEllen J Pritham
Department of Biology, University of Texas, Arlington, Arlington, TX 76019, USA
J Hered 100:648-55. 2009..The focus of this review is the discussion of some of the forces that act to shape transposable element diversity within and between genomes...
- Identification and functional characterization of cis-regulatory elements in the apicomplexan parasite Toxoplasma gondiiNandita Mullapudi
Department of Genetics, University of Georgia, East Green Street, Athens, Georgia 30602, USA
Genome Biol 10:R34. 2009..We have approached the question of gene regulation from a sequence perspective by mining the genomic sequence data to identify putative cis-regulatory elements using a de novo approach...
- A new single-step PCR assay for the detection of the zoonotic malaria parasite Plasmodium knowlesiNaomi W Lucchi
Atlanta Research and Education Foundation, Decatur, Georgia, United States of America
PLoS ONE 7:e31848. 2012..To address the need for more sensitive and specific diagnostic tests for the accurate diagnosis of P. knowlesi, we report development of a new single-step PCR assay that uses novel genomic targets to accurately detect this infection...