The expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels with distinct roles in synaptic transmission at the neuromuscular junction, the central and peripheral nervous system, and the inner ear. Remarkably, the complement of nAChR subunits has been highly conserved along vertebrate phylogeny. To ask whether the different subtypes of receptors underwent different evolutionary trajectories, we performed a comprehensive analysis of vertebrate nAChRs coding sequences, mouse single-cell expression patterns, and comparative functional properties of receptors from three representative tetrapod species. We found significant differences between hair cell and neuronal receptors that were most likely shaped by the differences in coexpression patterns and coassembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater coexpression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow coexpression pattern, and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.

中文翻译：

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神经元和毛细胞烟碱乙酰胆碱受体的不同进化轨迹。

离子通道家族的扩展和修剪在神经系统的进化中起着至关重要的作用。烟碱乙酰胆碱受体（nAChRs）是配体门控的离子通道，在神经肌肉接头，中枢神经系统和周围神经系统以及内耳的突触传递中具有独特的作用。值得注意的是，nAChR亚基的补体在脊椎动物系统发育中一直高度保守。为了询问受体的不同亚型是否经历了不同的进化轨迹，我们对脊椎动物的nAChRs编码序列，小鼠单细胞表达模式以及来自三种代表性四足动物的受体的比较功能特性进行了全面分析。我们发现毛细胞和神经元受体之间的显着差异很可能是由组成亚基的共表达模式和共装配规则的差异所决定的。因此，神经元nAChRs表现出高度的编码序列保守性，再加上更大的共表达差异和跨四足动物进化枝的功能特性的保守性。相反，毛细胞α9α10nAChRs表现出更大的序列差异，狭窄的共表达模式以及物种间功能特性的巨大差异。这些结果表明，在基因旁系同源物家族中，随机变化的差异底物与nAChR在突触传递中的分离作用有关。加上更大的共表达差异和跨四足动物进化枝的功能特性的保守性。相反，毛细胞α9α10nAChRs表现出更大的序列差异，狭窄的共表达模式以及物种间功能特性的巨大差异。这些结果表明在基因旁系同源物家族中随机变化的不同底物与nAChR在突触传递中的分离作用有关。加上更大的共表达差异和跨四足动物进化枝的功能特性的保守性。相反，毛细胞α9α10nAChRs表现出更大的序列差异，狭窄的共表达模式以及物种间功能特性的巨大差异。这些结果表明，在基因旁系同源物家族中，随机变化的差异底物与nAChR在突触传递中的分离作用有关。