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 Ka/Ks (the ratio between nonsynonymous and synonymous substitution rates) displays distinct profiles along the coding regions of MRG, with peaks (Ka/Ks > 1) corresponding to extracellular domains, and valleys (Ka/Ks < 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 nucleotide 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.
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机译：MRG基因家族（也称为SNSR）属于G蛋白偶联受体（GPCR）超家族，在伤害感受神经元中特异性表达，并参与伤害感受的调节。在这里，我们显示Ka / Ks（非同义替换率和同义替换率之间的比率）沿MRG的编码区域显示出不同的轮廓，其中的峰（Ka / Ks> 1）对应于胞外域，而谷点（Ka / K s <1）对应于跨膜和胞质结构域。细胞外结构域的特征还在于显着过量的自由基氨基酸变化。统计分析表明，到目前为止，正选择是最能解释 MRG 中核苷酸取代模式的模型。总之，这些结果表明，可能参与配体结合的MRG受体家族的胞外域经历了强烈的正选择。这种选择可能旨在改变伤害性神经元对厌恶刺激的敏感性和/或选择性。因此，我们的发现表明疼痛感知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水平。
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