Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events
Abstract
Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in metazoans. Importantly, we demonstrate that GluRs have followed different evolutionary histories in separated animal lineages. Our analysis reveals that the present organization of iGluRs into six classes does not capture the full complexity of their evolution. Instead, we propose an organization into four subfamilies and ten classes, four of which have never been previously described. Furthermore, we report a sister class to mGluR classes I-III, class IV. We show that many unreported proteins are expressed in the nervous system, and that new Epsilon receptors form functional ligand-gated ion channels. We propose an updated classification of glutamate receptors that includes our findings.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, Figure 1 - figure supplement 1, Figure 1 - figure supplement 3, Figure 1 - figure supplement 4, Figure2, Figure 4, Figure 4 - figure supplement 1 and Figure 4 - figure supplement 3.
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Article and author information
Author details
Funding
Ministerio de Economía y Competitividad (BFU2012-34398)
- David Ramos-Vicente
- Gemma Gou
- Rita Reig-Viader
- Javier Luís
- Àlex Bayés
Ministerio de Economía y Competitividad (BFU2014-57562-P)
- David Soto
Centre National de la Recherche Scientifique (ANR-16-CE12-0008-01)
- Hector Escriva
Ministerio de Economía y Competitividad (BFU2017-83317-P)
- David Soto
Ministerio de Economía y Competitividad (RD16/0008/0014)
- David Soto
Ministerio de Economía y Competitividad (BFU2015-69717-P)
- David Ramos-Vicente
- Gemma Gou
- Rita Reig-Viader
- Javier Luís
- Àlex Bayés
Seventh Framework Programme (304111)
- David Ramos-Vicente
- Gemma Gou
- Rita Reig-Viader
- Javier Luís
- Àlex Bayés
Ministerio de Economía y Competitividad (RYC-2011-08391)
- Àlex Bayés
Ministerio de Economía y Competitividad (RYC-2010-06210)
- Nerea Roher
China Scholarship Council (CSC-2013-06300075)
- Jie Ji
Ministerio de Economía y Competitividad (SAF2014-57994-R)
- Pablo Fuentes-Prior
Ministerio de Economía y Competitividad (AGL2015-65129-R)
- Jie Ji
- Nerea Roher
Generalitat de Catalunya (SGR-345-2014)
- David Ramos-Vicente
- Gemma Gou
- Rita Reig-Viader
- Javier Luís
- Àlex Bayés
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Leon D Islas, Universidad Nacional Autónoma de México, Mexico
Version history
- Received: February 9, 2018
- Accepted: November 20, 2018
- Accepted Manuscript published: November 22, 2018 (version 1)
- Version of Record published: December 27, 2018 (version 2)
Copyright
© 2018, Ramos-Vicente et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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