Evolution of the class C GPCR Venus flytrap modules involved positive selected functional divergence.
Evolution of the class C GPCR Venus flytrap modules involved positive selected functional divergence.
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C 类 GPCR 捕蝇草模块的进化涉及正选择功能分歧
DOI：
10.1186/1471-2148-9-67
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发表时间：
2009-03-27
影响因子：
3.4
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Cao J;Huang S;Qian J;Huang J;Jin L;Su Z;Yang J;Liu J
C类G蛋白偶联受体（GPCR）是GPCR家族中一个独特的群体，在结构上具有独特的胞外结构域，包括捕蝇草模块（VFTM）。C类gpcr的VFTMs负责配体识别和结合，并与细菌周围质氨基酸结合蛋白（PBPs）具有序列相似性。通过分析五组典型的C类gpcr的功能差异和阳性选择测试，对VFTMs进行了广泛的系统发育研究。改变的选择约束被确定，以确定通过正选择经历功能分化的位点。为了从结构上展示进化过程中的模式变化，对GPCR vftm的三维（3D）结构进行了建模和重建。结果我们的研究结果表明，C类gpcr的VFTMs中选择性约束的改变具有统计学意义。这意味着功能分化在基因复制事件后vftm的功能特征中发挥了关键作用。同时，正选择参与了进化过程，并推动了vftm的功能分化。我们的研究结果还表明，为了塑造C类gpcr的进化拓扑结构，发生了三个连续的重复事件。五组C类gpcr在功能分化中具有本质上不同的位点，这可能塑造了VFTMs的特定结构和功能。综上所述，我们的研究结果表明，功能分化涉及正选择，并部分负责C类GPCR VFTMs的进化模式。功能分化涉及的位点将为进一步研究这些模块的结构-功能关系以及揭示C类gpcr的激活机制提供更多线索和候选物。
BackgroundClass C G protein-coupled receptors (GPCRs) represent a distinct group of the GPCR family, which structurally possess a characteristically distinct extracellular domain inclusive of the Venus flytrap module (VFTM). The VFTMs of the class C GPCRs is responsible for ligand recognition and binding, and share sequence similarity with bacterial periplasmic amino acid binding proteins (PBPs). An extensive phylogenetic investigation of the VFTMs was conducted by analyzing for functional divergence and testing for positive selection for five typical groups of the class C GPCRs. The altered selective constraints were determined to identify the sites that had undergone functional divergence via positive selection. In order to structurally demonstrate the pattern changes during the evolutionary process, three-dimensional (3D) structures of the GPCR VFTMs were modelled and reconstructed from ancestral VFTMs.ResultsOur results show that the altered selective constraints in the VFTMs of class C GPCRs are statistically significant. This implies that functional divergence played a key role in characterizing the functions of the VFTMs after gene duplication events. Meanwhile, positive selection is involved in the evolutionary process and drove the functional divergence of the VFTMs. Our results also reveal that three continuous duplication events occurred in order to shape the evolutionary topology of class C GPCRs. The five groups of the class C GPCRs have essentially different sites involved in functional divergence, which would have shaped the specific structures and functions of the VFTMs.ConclusionTaken together, our results show that functional divergence involved positive selection and is partially responsible for the evolutionary patterns of the class C GPCR VFTMs. The sites involved in functional divergence will provide more clues and candidates for further research on structural-function relationships of these modules as well as shedding light on the activation mechanism of the class C GPCRs.
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影响因子：
5.8
作者：
Catherinot, V;Labesse, G
通讯作者：
Labesse, G
影响因子：
4.8
作者：
Cuneo, Matthew J.;Changela, Anita;Hellinga, Homme W.
通讯作者：
Hellinga, Homme W.
影响因子：
30.8
作者：
McLysaght, A;Hokamp, K;Wolfe, KH
通讯作者：
Wolfe, KH
影响因子：
10.7
作者：
Gu, X
通讯作者：
Gu, X
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE