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The origin and evolution of synapses

Nature Reviews Neuroscience volume 10, pages 701–712 (2009)Cite this article

A Corrigendum to this article was published on 01 November 2009

Key Points

  • The molecular composition of the synapse has recently been proved to be useful for studying the evolution of the brain.

  • Synapse proteomics data sets, such as those of the postsynaptic density (PSD) and associated protein complexes when combined with comparative genomics have provided unprecedented insights into the evolution of synapses.

  • The PSD that is found in organisms with nervous systems has evolved from an ancient protosynaptic core that exists in unicellular organisms and multicellular organisms without nervous systems.

  • Comparisons of vertebrate PSD and synaptogenesis genes with orthologues from sponges and cnidarians open an avenue for speculating as to what may have contributed to the origin of the first synapse.

  • Comparative proteomics has shown that vertebrate excitatory synapses have evolved to be significantly more complex than invertebrates.

Abstract

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Understanding the evolutionary origins of behaviour is a central aim in the study of biology and may lead to insights into human disorders. Synaptic transmission is observed in a wide range of invertebrate and vertebrate organisms and underlies their behaviour. Proteomic studies of the molecular components of the highly complex mammalian postsynaptic machinery point to an ancestral molecular machinery in unicellular organisms — the protosynapse — that existed before the evolution of metazoans and neurons, and hence challenges existing views on the origins of the brain. The phylogeny of the molecular components of the synapse provides a new model for studying synapse diversity and complexity, and their implications for brain evolution.

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Figure 1: Phylogenetic tree depicting taxons of current relevance to synapse evolution.
Figure 2: Evolution of postsynaptic components.
Figure 3: Comparative proteomics of mouse and Drosophila melanogaster MASC.
Figure 4: NMDA receptor carboxy-terminal evolution.
Figure 5: MASC signalling diversity within the brain.

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Acknowledgements

We thank members of the Genes to Cognition Programme for useful discussions. T.J.R. was supported by a Wellcome Trust Ph.D. Studentship at time of writing.

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Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK

    Tomás J. Ryan & Seth G. N. Grant

  2. Wolfson College, University of Cambridge, Barton Road, CB3 9BB, Cambridge, UK

    Tomás J. Ryan

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  1. Tomás J. Ryan
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Correspondence to Seth G. N. Grant.

Supplementary information

Supplementary information S1 (table)

Protein classes in mouse PSD and MASC (PDF 84 kb)

Supplementary information S2 (Box)

The phylogenetic history of Porifera (sponges) (PDF 111 kb)

Supplementary information S3 (Box)

GABA and metabotropic receptors in Dictyostelium discoideum (PDF 130 kb)

Related links

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FURTHER INFORMATION

Seth G. N. Grant's homepage

Timetree

Glossary

Postsynaptic proteome

The complete set of proteins currently identified at the postsynaptic side of the synapse.

MAGUK

Membrane-associated guanylate kinase (MAGUK) proteins act as scaffolds for the clustering of receptors, ion channels and associated signalling proteins at postsynaptic sites.

Ursynapse

The last common ancestor of all synapses. This was the platform from which diversity of synaptic proteins between different organisms and different synapse types evolved.

Orthologues

Homologous genes that separated due to a speciation event.

Protosynapse

Those synaptic components that were present before the emergence of synapses and most likely contributed to their evolution.

Bilaterians

Animals belonging to the phylum Bilateria. These are a clade of animals with bilateral symmetry that possess complex nervous systems. They are divided into protostomes and deuterostomes.

Outgroup

A group of organisms that serves as a reference group for determination of the evolutionary relationship between monophyletic groups of organisms.

Choanoflagellates

Organisms belonging to the phylum Choanoflagellata. These are unicellular eukaryotes that can exist in both free-living and colonial forms, and are multicellular metazoans considered to be the closest unicellular relative of multicellular metazoans.

Porifera

Phylum of multicellular animals (poriferans or sponges) that lack a nervous system.

Demosponge

Organism belonging to the primary class of Porifera. Demosponges account for ∼90% all sponge species.

Cnidarian

Animal belonging to the phylum Cnidaria. Cnidarians are animals with radial symmetry including jellyfish, coral, hyrda and anemones. Cnidarian nervous systems consist of diffuse neuronal net-like structures.

Clade

An evolutionary group consisting of a given single common ancestor and all of its descendants.

Protostomes

Animals belonging to the phylum Protostomia, an animal clade that includes the superphyla Ecdysozoa (arthropods and nematodes) and Lophotrochozoa.

Deuterostomes

Animals belonging to the superphylum Deuterostomia that includes the subphylum Vertebrata.

Homologues

Set of genes or proteins that are related by descent, that is, they share a common ancestor.

Genome duplication

Duplication of an entire genome that results in an abundance of duplicated genes, most of which are lost. Two rounds of genome duplication are believed to have occurred at the base of the chordate lineage.

Gene duplication

Duplication of a given gene owing to replication errors and resulting in two redundant copies of the original gene.

Paralogues

Homologous genes that separated because of a gene duplication event.

Immunological synapse

A region that can form between two cells of the immune system in close contact. The immunolgical synapse originally reffered to the interaction between a T cell and an antigen-presenting cell.

Positive selection

Positive selection is said to occur when a given genetic variant rises to prevalence in a population by increasing the reproductive fitness of the organism in a given environment. Positive selection at the level of amino acid sequence is identified by the dN/dS ratio.

Non-synonymous nucleotide substitution

A nucleotide substitution in the coding sequence of a gene that alters the amino acid sequence of the protein.

Synonymous nucleotide substitution

A nucleotide substitution in the coding sequence of a gene that does not alter the amino acid sequence of the protein.

dN/dS ratio

The ratio of non-synonymous nucleotide substitutions to synonymous nucleotide substitution for a given protein-coding gene. A dN/dS ratio of <1 implies purifying selection or conservative evolution, ∼0 implies relaxation of constraint or neutral evolution, >1 implies positive selection or adaptive evolution. This measure is based on Kimura's theory of molecular evolution, which argues that the vast majority of nucleotide sequence changes are functionally neutral.

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Ryan, T., Grant, S. The origin and evolution of synapses. Nat Rev Neurosci 10, 701–712 (2009). https://doi.org/10.1038/nrn2717

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