Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors

PLoS One. 2016 Mar 17;11(3):e0151934. doi: 10.1371/journal.pone.0151934. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Archaea / classification
  • Archaea / genetics
  • Archaea / physiology
  • Conserved Sequence / genetics
  • Conserved Sequence / physiology
  • Cysteine Loop Ligand-Gated Ion Channel Receptors / genetics
  • Cysteine Loop Ligand-Gated Ion Channel Receptors / physiology
  • Eukaryota / genetics
  • Eukaryota / physiology
  • Evolution, Molecular
  • Fungi / genetics
  • Fungi / physiology
  • Invertebrates / genetics
  • Invertebrates / physiology
  • Ligand-Gated Ion Channels / genetics*
  • Ligand-Gated Ion Channels / physiology
  • Phylogeny
  • Plants / genetics
  • Receptors, Neurotransmitter / genetics*
  • Receptors, Neurotransmitter / physiology
  • Sequence Alignment

Substances

  • Cysteine Loop Ligand-Gated Ion Channel Receptors
  • Ligand-Gated Ion Channels
  • Receptors, Neurotransmitter

Grants and funding

Agence Nationale de la Recherche grant PentaGate (http://www.agence-nationale-recherche.fr/?Projet=ANR-13-BSV8-0020) benefitted all three authors by funding missions for AT and JH and a stipend for MJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.