title: Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.
abstract: 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.
authors.affiliation: Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS and Université Paris Diderot, Paris, France.
authors.forename: Mariama
authors.initials: M
authors.lastname: Jaiteh
authors.affiliation: Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS and Université Paris Diderot, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Taly
authors.affiliation: Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS and Université Paris Diderot, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hénin
mesh_terms: D000818:Animals; D001105:Archaea / Q000145:classification / Q000235:genetics / Q000502:physiology; D017124:Conserved Sequence / Q000235:genetics / Q000502:physiology; D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors / Q000235:genetics / Q000502:physiology; D056890:Eukaryota / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D005658:Fungi / Q000235:genetics / Q000502:physiology; D007448:Invertebrates / Q000235:genetics / Q000502:physiology; D058446:Ligand-Gated Ion Channels / Q000235:genetics* / Q000502:physiology; D010802:Phylogeny; D010944:Plants / Q000235:genetics; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment
chemical_list: D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors; D058446:Ligand-Gated Ion Channels; D017981:Receptors, Neurotransmitter