Adaptive evolution of MRG, a neuron-specific gene family implicated in nociception
Adaptive evolution of MRG, a neuron-specific gene family implicated in nociception
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DOI：
10.1101/gr.1431603
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发表时间：
2003-10-01
期刊：
影响因子：
7
通讯作者：
Lahn, BT
中科院分区：
文献类型：
--
作者：
Choi, SS;Lahn, BT
MRG基因家族(又称SNSR)属于G蛋白偶联受体(GPCR)超家族，在伤害性神经元中特异表达，参与伤害性感觉的调节。在这里，我们发现K-a/K-S(非同义和同义替换率之比)沿着MRG的编码区显示出不同的图谱，峰值(K-a/K-S>；1)对应于胞外结构域，山谷(K-a/K-S<；1)对应于跨膜和细胞质结构域。胞外区的特征还包括显著过量的自由基氨基酸变化。统计分析表明，正选择是迄今为止最适合解释MRG中核苷酸替换模式的模型。综上所述，这些结果表明，可能参与配体结合的MRG受体家族的胞外结构域经历了强烈的正向选择。这种选择可能是为了改变伤害性神经元对厌恶刺激的敏感性和/或选择性。因此，我们的发现表明，痛觉是神经系统的一个方面，可能经历了令人惊讶的适应性进化。
The MRG gene family (also known as SNSR) belongs to the G-protein-coupled receptor (GPCR) superfamily, is expressed specifically in nociceptive neurons, and is implicated in the modulation of nociception. Here, we show that K-a/K-s (the ratio between nonsynonymous and synonymous substitution rates) displays distinct profiles along the coding regions of MRG, with peaks (K-a/K-s > 1) corresponding to extracellular domains, and valleys (K-a/K-s < 1) corresponding to transmembrane and cytoplasmic domains. The extracellular domains are also characterized by a significant excess of radical amino acid changes. Statistical analysis shows that positive selection is by far the most suitable model to account for the nucleoticle substitution patterns in MRG. Together, these results demonstrate that the extracellular domains of the MRG receptor family, which presumably partake in ligand binding, have experienced strong positive selection. Such selection is likely directed at altering the sensitivity and/or selectivity of nociceptive neurons to aversive stimuli. Thus, our finding Suggests pain perception as an aspect of the nervous system that may have experienced a surprising level of adaptive evolution.