Jaiteh Mariama, Taly Antoine, Hénin Jérôme
Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS and Université Paris Diderot, Paris, France.
PLoS One. 2016 Mar 17;11(3):e0151934. doi: 10.1371/journal.pone.0151934. eCollection 2016.
Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such "Cys-less" receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the "Cys-loop" proline is absolutely conserved, suggesting the more fitting name "Pro loop" for that motif, and "Pro-loop receptors" for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.
五聚体配体门控离子通道（pLGICs）是两侧对称动物中普遍存在的神经递质受体，已知有少量原核生物同源物。在此，我们描述了对所有生命王国中pLGIC基因的新清查和系统发育分析。我们的主要发现是单细胞真核生物中有一组pLGIC基因，其中一些是后生动物样的半胱氨酸环受体，而另一些则没有半胱氨酸环半胱氨酸，类似于它们的原核生物亲属。许多这样的“无半胱氨酸”受体也出现在无脊椎动物后生动物中。这些发现共同描绘了pLGICs在真核生物中的新分布。原核通道的分布也更加广泛，包括一个主要的新古菌类群，奇古菌门。更普遍地说，除了多细胞植物和真菌外，pLGICs现在在主要分类群中几乎无处不在。然而，pLGICs在单细胞类群中稀少存在，这表明基因丢失率很高且具有非必需特征，这与它们作为两侧对称动物神经系统突触受体的重要作用形成对比。这些高度不同序列的多重比对揭示了少量保守残基聚集在细胞外和跨膜结构域之间的界面处。只有“半胱氨酸环”脯氨酸是绝对保守的，这表明该基序更合适的名称是“脯氨酸环”，而该超家族则称为“脯氨酸环受体”。推断的分子系统发育显示真核生物中有一个半胱氨酸环和一个无半胱氨酸分支，两者都包含后生动物和单细胞成员。这提出了关于该超家族进化历史的新假设，例如半胱氨酸环半胱氨酸可能起源于古代单细胞真核生物。更深层次的系统发育关系仍然不确定，特别是在细菌、古菌和真核生物之间的分化周围。
