Association of the Plasmodium falciparuminfected erythrocyte surface molecule with ist virulence
| Project/Area Number |
17406009
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Nagasaki University (2007)
Ehime University (2005-2006) |
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Principal Investigator |
KANEKO Osamu Nagasaki University, Institute of Tropical Medicine, Department of Protozoology, Professor (50325370)
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| Co-Investigator(Kenkyū-buntansha) |
TORII Motomi Ehime University, Graduate School of Medicine, Department of Molecular Parasitology, Professor (20164072)
TACHIBANA Mayumi Ehime University, Graduate School of Medicine, Department of Molecular Parasitology, Assistant Professor (00301325)
OTSUKI Hitoshi Ehime University, Graduate School of Medicine, Department of Molecular Parasitology, Assistant Professor (80403806)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,660,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2007: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Infectious Disease / Parasite / Genetic polymorphism / Antigenic variation |
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| Research Abstract |
Plasmodium falciparum SURFIN is a polymorphic antigen localized at the apical end of the merozoite, and on the surface of infected erythrocytes. In an analysis using laboratory line parasites, the N-terminal extracellular region was shown to be highly polymorphic. In order to investigate the level of polymorphism in wild isolates, and to assess whether this region is under positive selection, we sequenced the 2167 by nucleotide (nt) encoding the extracellular domain of SURFIN4.2 from P falciparum field isolates collected in Thailand at two different time points. Twenty-one sequences were analyzed from samples collected in 1988/1989 and 32 sequences from 2003/2005. A total of 258 polymorphic sites were observed with an average nucleotide diversity of 0.043. Based on the predicted protein structure and the level of polymorphism, we divided the extracellular region into three parts; a Cysteine-rich domain (nt 1-585), variable domain 1 (nt 586-1392) and variable domain 2 (nt 1393-2194). The majority of polymorphic sites were clustered in variable domain 2. An excess of nonsynonymous substitutions over synonymous substitutions was detected in all regions, suggesting that positive selection is acting throughout the extracellular region. Tajima's D test and Fu & Li's D^* and F^* tests all detected the signature of positive selection on variable domain 2 at the 99% confidence level. Thus, the extracellular domain of SURFIN_4.2 appears to have evolved under positive diversifying selection, possibly mediated by host immune pressure. There are no correlation between virulence and particular amino acid substitution. When the amino acid frequency was compared at each amino acid position between samples in 1988/1989 and 2003/2005, most positions showed same C291frequency except 4 positions. Further evaluation is needed to confirm this observation.
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Report
(4 results)
Research Products
(13 results)
