Glutamate Receptors: Family matters

Genome sequence data from a range of animal species are raising questions about the origins of glutamate receptors.
  • Download
  • Cite
  • CommentOpen annotations (there are currently 0 annotations on this page).
  1. Mark L Mayer  Is a corresponding author
  2. Timothy Jegla  Is a corresponding author
  1. National Institute for Neurological Disorders and Stroke, United States
  2. Pennsylvania State University, United States

Receptors for the amino acid glutamate have a crucial role in the nervous system of nearly all animals. These proteins are split between two families: metabotropic glutamate receptors modulate the activity of neural networks, while ionotropic glutamate receptors mediate the transmission of signals between neurons. While we know a great deal about glutamate receptors, the gigabytes of data from recent genome sequencing projects provide a new opportunity to dissect how they have evolved.

These growing genomic data have also prompted new ideas about the evolution of animals. According to a new – and still controversial – version of the animal tree of life (Figure 1), comb jellies, or ctenophores, evolved first (Moroz et al., 2014; Ryan et al., 2013). Sponges (porifera) appeared next, followed by placozoans, jellyfishes (cnidarians) and, finally, bilaterians, vertebrates and invertebrates with bilateral body symmetry. If this revised tree is correct (Jékely et al., 2015; Ryan, 2014), neurons could have been lost twice during evolution because comb jellies have a nervous system but sponges and placozoans do not. Now, in eLife, Àlex Bayés of the Biomedical Research Institute Sant Pau in Barcelona and colleagues – including David Ramos-Vicente as first author – report new insights into the evolution of glutamate receptors by conducting a comprehensive study of these proteins across different animal groups (Ramos-Vicente et al., 2018).

Two models for the evolution of glutamate receptors.

(A) For many years, it was assumed that porifera (sponges) were the earliest animals, but some researchers now argue that instead, ctenophores (comb jellies) evolved first. Yet, the details of how …

Previously, researchers had identified four sub-families of ionotropic glutamate receptors, but they had mainly looked at vertebrate species. Now, Ramos-Vicente et al. muster data from other animal groups and propose a major reclassification that contains two new sub-families called Epsilon and Lambda. The NMDA receptors, which play a special role in vertebrates (Collingridge and Bliss, 1995), remain from the old classification, and the AKDF sub-family combines three other sub-families from the former model. Moreover, the team argues that all four sub-families were present in the last common ancestor of animals, with some being lost repeatedly during evolution (Figure 1A).

This would explain why the Epsilon sub-family is present in most animals today, whereas Lambda is only found in sponges. AKDF is carried by sponges, placozoans, jellyfish and bilaterians, but NMDA receptors exist only in these last two groups. However, we favor an alternative model in which the Epsilon sub-family evolved first, followed by the AKDF proteins. The Lambda receptors came next but only in sponges; then finally, the NMDA sub-family emerged in a common ancestor of jellyfish and bilaterians, persisting in these species (Figure 1B).

Amongst the newly identified sub-families, the Epsilon receptors are especially interesting because, like NMDA receptors, some of them are activated by glycine and others by glutamate. Such glycine receptors have previously been found in comb jellies (Alberstein et al., 2015; Yu et al., 2016), and now Ramos-Vicente et al. have identified them in a group of bilateral animals called lancelets, even though these organisms are separated from comb jellies by hundreds of millions of years of evolution. The receptors that get activated by glycine were more widespread than expected, with three receptors preferring glycine for every two favoring glutamate.

Deciphering the genetic sequence of a protein helps to predict its final structure. These analyses revealed that in comb jellies and lancelets, a subset of ionotropic glutamate receptors lacks the molecular features required to bind neurotransmitter amino acids, which suggests that they attach to other, as yet unidentified molecules. Surprisingly, when modeling the structure of one of the Epsilon receptors found in lancelets, it appeared that it might not be able to bind a ligand at all. This feature was seen in five Epsilon subunits and six AKDF subunits in these animals.

Many of the new receptors reported by Ramos-Vicente et al. have been identified only by analyzing their genetic sequences; their functional properties have yet to be studied either in native tissues, which is a challenge for many marine creatures, or by expressing these proteins in model organisms. When this is done, our understanding of the diversity of glutamate receptors will expand enormously.

References

Article and author information

Author details

  1. Mark L Mayer

    Mark L Mayer is at the National Institute for Neurological Disorders and Stroke, Bethesda, United States

    For correspondence
    mark.mayer@nih.gov
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4378-8451
  2. Timothy Jegla

    Timothy Jegla is in the Department of Biology and the Huck Institute for the Life Sciences, Pennsylvania State University, University Park, United States

    For correspondence
    tjj3@psu.edu
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8616-2390

Publication history

  1. Version of Record published:

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,591
    views
  • 2
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

Further reading

    1. Evolutionary Biology
    Ljiljana Mihajlovic, Bharat Ravi Iyengar ... Yolanda Schaerli
    Research Article

    Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.

    1. Evolutionary Biology
    Lucy A Winder, Mirre JP Simons, Terry Burke
    Research Article

    Life-history theory, central to our understanding of diversity in morphology, behaviour, and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness – reproductive effort and survival – questioning the theory’s general validity. We used a meta-analysis to separate the effects of individual quality (positive survival/reproduction correlation) from the costs of reproduction (negative survival/reproduction correlation) using studies of reproductive effort and parental survival in birds. Experimental enlargement of brood size caused reduced parental survival. However, the effect size of brood size manipulation was small and opposite to the effect of phenotypic quality, as we found that individuals that naturally produced larger clutches also survived better. The opposite effects on parental survival in experimental and observational studies of reproductive effort provide the first meta-analytic evidence for theory suggesting that quality differences mask trade-offs. Fitness projections using the overall effect size revealed that reproduction presented negligible costs, except when reproductive effort was forced beyond the maximum level observed within species, to that seen between species. We conclude that there is little support for the most fundamental life-history trade-off, between reproductive effort and survival, operating within a population. We suggest that within species the fitness landscape of the reproduction–survival trade-off is flat until it reaches the boundaries of the between-species fast–slow life-history continuum. Our results provide a quantitative explanation as to why the costs of reproduction are not apparent and why variation in reproductive effort persists within species.