| Project/Area Number |
21590356
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAKAJIMA Toshiaki 東京医科歯科大学, 大学院・疾患生命科学研究部, 准教授 (50307956)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Akinori 東京医科歯科大学, 難治疾患研究所, 教授 (60161551)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子遺伝学 / TLR(Toll-like receptor) / エンドトキシン / 霊長類 / バージャー病 / TLR (Toll-like receptor) |
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| Research Abstract |
The innate immune system constitutes the front line of host defense against pathogens. Toll-like receptor 4(TLR4) recognize molecules derived from pathogens and play crucial roles in the innate immune system. Here we provide evidence that the TLR4 gene have come under natural selection pressure in the course of primate evolution. We compared the nucleotide sequences of TLR4 gene among seven primate species. Analysis of the non-synonymous/synonymous substitution ratio revealed the presence of both strictly conserved and rapidly evolving regions in the TLR4 gene. The genomic segments encoding the intracellular Toll/interleukin 1 receptor(TIR) domains, which exhibited lower rates of non-synonymous substitution, have undergone purifying selection. In contrast, the extracellular domain of TLR4, which carried an unusually high proportion of non-synonymous substitutions, was found to have been the target of positive Darwinian selection in primate evolution. However, the 3D structural prediction showed no difference in the 3D structure of extracellular domain of TLR4 among seven primate species. We also reported the association of MYD88 with the susceptibility to Buerger's disease.
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