Browsing by Author "Patrath Ponsuwanna"

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    Analysis of the polymorphic SER gene family in Tetrahymena Thermophila
    (Mahidol University. Mahidol University Library and Knowledge Center, 2023) Patrath Ponsuwanna; Thanat Chookajorn; Sumalee Tungpradabkul; Wilai Noonpakdee
    Tetrahymena thermophila, a free-living ciliate, displays immobilization antigens (i-ag) on its surface. These proteins are cysteine-rich and are linked to the membrane by a glycosylphosphatidylinositol (GPI) anchor. They are encoded by a family of polymorphic Ser genes. Thirteen Ser genes were characterized so far, representing only a portion of the reported i-ag. Characterization of Ser gene family is impeded by its sequence polymorphism. In this study an algorithm to select Ser candidate from T. thermophila MAC genome was developed. The Ser prediction algorithm exploited two characteristic features of Ser---repetitive cysteine pattern and GPI anchor signal. The algorithm successfully selected Ser candidates including known Ser. Ser candidates were compared to known Ser and classified into subtypes by phylogenetic analysis. Ser candidates were found to be located as gene tandem array, suggesting that Ser gene family expands via gene duplication. Ser genes located on the same tandem array may have similar gene expression profile. The Ser prediction algorithm can select Ser candidates that did not belong to previously characterized subtype. Because the algorithm does not rely on sequence similarity, it can perform Ser identification more extensively than the sequence homology approach.
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    Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites
    (2016-01-29) Patrath Ponsuwanna; Theerarat Kochakarn; Duangkamon Bunditvorapoom; Krittikorn Kümpornsin; Thomas D. Otto; Chase Ridenour; Kesinee Chotivanich; Prapon Wilairat; Nicholas J. White; Olivo Miotto; Thanat Chookajorn; Mahidol University; Faculty of Medicine, Siriraj Hospital, Mahidol University; Wellcome Trust; Nuffield Department of Clinical Medicine; Wellcome Trust Sanger Institute; University of Oxford
    © 2016 Ponsuwanna et al. Background: Malaria parasites have evolved a series of intricate mechanisms to survive and propagate within host red blood cells. Intra-erythrocytic parasitism requires these organisms to digest haemoglobin and detoxify iron-bound haem. These tasks are executed by haemoglobin-specific proteases and haem biocrystallization factors that are components of a large multi-subunit complex. Since haemoglobin processing machineries are functionally and genetically linked to the modes of action and resistance mechanisms of several anti-malarial drugs, an understanding of their evolutionary history is important for drug development and drug resistance prevention. Methods: Maximum likelihood trees of genetic repertoires encoding haemoglobin processing machineries within Plasmodium species, and with the representatives of Apicomplexan species with various host tropisms, were created. Genetic variants were mapped onto existing three-dimensional structures. Genome-wide single nucleotide polymorphism data were used to analyse the selective pressure and the effect of these mutations at the structural level. Results: Recent expansions in the falcipain and plasmepsin repertoires are unique to human malaria parasites especially in the Plasmodium falciparum and P. reichenowi lineage. Expansion of haemoglobin-specific plasmepsins occurred after the separation event of Plasmodium species, but the other members of the plasmepsin family were evolutionarily conserved with one copy for each sub-group in every Apicomplexan species. Haemoglobin-specific falcipains are separated from invasion-related falcipain, and their expansions within one specific locus arose independently in both P. falciparum and P. vivax lineages. Gene conversion between P. falciparum falcipain 2A and 2B was observed in artemisinin-resistant strains. Comparison between the numbers of non-synonymous and synonymous mutations suggests a strong selective pressure at falcipain and plasmepsin genes. The locations of amino acid changes from non-synonymous mutations mapped onto protein structures revealed clusters of amino acid residues in close proximity or near the active sites of proteases. Conclusion: A high degree of polymorphism at the haemoglobin processing genes implicates an imposition of selective pressure. The identification in recent years of functional redundancy of haemoglobin-specific proteases makes them less appealing as potential drug targets, but their expansions, especially in the human malaria parasite lineages, unequivocally point toward their functional significance during the independent and repetitive adaptation events in malaria parasite evolutionary history.
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    Comparative genome‑wide analysis and evolutionary history of haemoglobin‑processing and haem detoxification enzymes in malarial parasites
    (2016) Patrath Ponsuwanna; Theerarat Kochakarn; Duangkamon Bunditvorapoom; Krittikorn Kümpornsin; Otto, Thomas D.; Chase Ridenour; Kesinee Chotivanich; Prapon Wilairat; White, Nicholas J.; Olivo Miotto; Thanat Chookajorn; Mahidol University. Faculty of Tropical Medicine. Genomic and Evolutionary Medicine Unit, Centre of Excellence in Malaria
    Background: Malaria parasites have evolved a series of intricate mechanisms to survive and propagate within host red blood cells. Intra-erythrocytic parasitism requires these organisms to digest haemoglobin and detoxify ironbound haem. These tasks are executed by haemoglobin-specific proteases and haem biocrystallization factors that are components of a large multi-subunit complex. Since haemoglobin processing machineries are functionally and genetically linked to the modes of action and resistance mechanisms of several anti-malarial drugs, an understanding of their evolutionary history is important for drug development and drug resistance prevention. Methods: Maximum likelihood trees of genetic repertoires encoding haemoglobin processing machineries within Plasmodium species, and with the representatives of Apicomplexan species with various host tropisms, were created. Genetic variants were mapped onto existing three-dimensional structures. Genome-wide single nucleotide polymorphism data were used to analyse the selective pressure and the effect of these mutations at the structural level. Results: Recent expansions in the falcipain and plasmepsin repertoires are unique to human malaria parasites especially in the Plasmodium falciparum and P. reichenowi lineage. Expansion of haemoglobin-specific plasmepsins occurred after the separation event of Plasmodium species, but the other members of the plasmepsin family were evolutionarily conserved with one copy for each sub-group in every Apicomplexan species. Haemoglobin-specific falcipains are separated from invasion-related falcipain, and their expansions within one specific locus arose independently in both P. falciparum and P. vivax lineages. Gene conversion between P. falciparum falcipain 2A and 2B was observed in artemisinin-resistant strains. Comparison between the numbers of non-synonymous and synonymous mutations suggests a strong selective pressure at falcipain and plasmepsin genes. The locations of amino acid changes from non-synonymous mutations mapped onto protein structures revealed clusters of amino acid residues in close proximity or near the active sites of proteases. Conclusion: A high degree of polymorphism at the haemoglobin processing genes implicates an imposition of selective pressure. The identification in recent years of functional redundancy of haemoglobin-specific proteases makes them less appealing as potential drug targets, but their expansions, especially in the human malaria parasite lineages, unequivocally point toward their functional significance during the independent and repetitive adaptation events in malaria parasite evolutionary history.
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    Genome-wide prediction of the polymorphic Ser gene family in Tetrahymena thermophila based on motif analysis
    (2014-08-18) Patrath Ponsuwanna; Krittikorn Kümpornsin; Thanat Chookajorn; Mahidol University
    Even though antigenic variation is employed among parasitic protozoa for host immune evasion, Tetrahymena thermophila, a free-living ciliate, can also change its surface protein antigens. These cysteine-rich glycosylphosphatidylinositol (GPI)-linked surface proteins are encoded by a family of polymorphic Ser genes. Despite the availability of T. thermophila genome, a comprehensive analysis of the Ser family is limited by its high degree of polymorphism. In order to overcome this problem, a new approach was adopted by searching for Ser candidates with common motif sequences, namely length-specific repetitive cysteine pattern and GPI anchor site. The candidate genes were phylogenetically compared with the previously identified Ser genes and classified into subtypes. Ser candidates were often found to be located as tandem arrays of the same subtypes on several chromosomal scaffolds. Certain Ser candidates located in the same chromosomal arrays were transcriptionally expressed at specific T. thermophila developmental stages. These Ser candidates selected by the motif analysis approach can form the foundation for a systematic identification of the entire Ser gene family, which will contribute to the understanding of their function and the basis of T. thermophila antigenic variation. © 2014 Ponsuwanna et al.
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    Mutually exclusive var gene expression in the malaria parasite: multiple layers of regulation
    (2008-10-01) Thanat Chookajorn; Patrath Ponsuwanna; Liwang Cui; Mahidol University; Pennsylvania State University
    As a major factor in Plasmodium falciparum malaria pathogenesis, the var gene family has been the focus of extensive research, which has contributed to our current understanding of Plasmodium antigenic variation. In recent years, sophisticated molecular tools have enabled the generation of interesting data regarding the regulation of mutually exclusive var expression. Although their results are still inconclusive, these studies have demonstrated the existence of multiple layers of control over gene activation, silencing, memory and 'counting'. This review attempts to summarize recent findings and dissect the different layers of var regulation. © 2008 Elsevier Ltd. All rights reserved.