Molecular evolution of the TLR4 gene in the course of primate evolution and their sensitivities to the response to endotoxin

灵长类动物进化过程中TLR4基因的分子进化及其对内毒素反应的敏感性

• 批准号: 21590356
• 负责人: NAKAJIMA Toshiaki
• 金额: $ 3万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590356/
• 关键词: 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)

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.

先天性免疫系统构成宿主防御病原体的最前线。Toll样受体4（TLR 4）识别来自病原体的分子，并在先天免疫系统中发挥关键作用。在这里，我们提供的证据表明，TLR 4基因在灵长类动物进化过程中受到自然选择的压力。比较了7种灵长类动物TLR 4基因的核苷酸序列。非同义/同义取代比率的分析揭示了TLR 4基因中存在严格保守和快速进化的区域。编码细胞内Toll/白细胞介素1受体（TIR）结构域的基因组片段，表现出较低的非同义取代率，已进行纯化选择。相比之下，TLR 4的胞外结构域，其中进行了异常高比例的非同义取代，被发现已在灵长类进化的达尔文选择的目标。然而，三维结构预测显示TLR 4胞外结构域的三维结构在7种灵长类动物中没有差异。我们还报道了MYD 88与Buerger病易感性的关系。

项目成果

Losartan inhibits LPS-induced inflammatory signaling by PPAR-gamma-dependent mechanism in human THP-1 macrophage.

氯沙坦通过人 THP-1 巨噬细胞中的 PPAR-γ 依赖性机制抑制 LPS 诱导的炎症信号传导。

• 发表时间: 2010
• 期刊: Hypertension Res.
• 作者: An J;Nakajima T;Kuba K;Kimura A
• 通讯作者: Kimura A

Comparative genomics : insight into human health and disease. In The HLA Complex in Biology and Medicine : aresource book

比较基因组学：洞察人类健康和疾病。

• 发表时间: 2009
• 作者: Nakajima T;Kimura A
• 通讯作者: Kimura A

Comparative genomics : insight into human health and disease. In The HLA Complex in Biology and Medicine : a resource book

比较基因组学：洞察人类健康和疾病。

• 发表时间: 2009
• 作者: Nakajima T;Kimura A
• 通讯作者: Kimura A

Toll-like receptor 2 gene polymorphisms associated with aggressive periodontitis in Japanese

Toll样受体2基因多态性与日本侵袭性牙周炎相关

• 发表时间: 2011
• 期刊: Open Dent J
• 影响因子: 1.3
• 作者: Takahashi M;Chen Z;Watanabe K;Kobayashi H;Nakajima T;Kimura A;Izumi Y
• 通讯作者: Izumi Y

Molecular evolution of immunoglobulin superfamily genes in primates

• DOI: 10.1007/s00251-011-0519-7
• 发表时间: 2011-07-01
• 期刊: IMMUNOGENETICS
• 影响因子: 3.2
• 作者: Ohtani, Hitoshi;Nakajima, Toshiaki;Kimura, Akinori
• 通讯作者: Kimura, Akinori