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.
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.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Kandel, E. R. The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038 (2001).
Hebb, D. The Organization of Behavior; a Neuropsychological Theory. (New York, Wiley,, 1949).
Morgan, C. L. Animal Life and Intelligence (E. Arnold, London, 1891).
Collins, M. O. et al. Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J. Neurochem. 97 (Suppl. 1), 16–23 (2006). A comprehensive collation of postsynaptic protein complexes
Bayes, A. & Grant, S. G. Neuroproteomics: understanding the molecular organization and complexity of the brain. Nature Rev. Neurosci. 10, 635–646 (2009). A detailed review on the state of the art of proteomics in neuroscience
Fernandez, E. et al. Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Mol. Syst. Biol. 5, 269 (2009).
Pocklington, A. J., Cumiskey, M., Armstrong, J. D. & Grant, S. G. The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour. Mol. Syst. Biol. 2, 2006 0023 (2006).
Grant, S. G., Marshall, M. C., Page, K. L., Cumiskey, M. A. & Armstrong, J. D. Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases. Hum. Mol. Genet. 14 Spec. No. 2, R225–234 (2005).
Round, J. L. et al. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-κB transcription factors. Nature Immunol. 8, 154–161 (2007).
Tsunoda, S. & Zuker, C. S. The organization of INAD-signaling complexes by a multivalent PDZ domain protein in Drosophila photoreceptor cells ensures sensitivity and speed of signaling. Cell Calcium 26, 165–171 (1999).
Wolfe, K. H. & Li, W. H. Molecular evolution meets the genomics revolution. Nature Genet. 33, S255–S265 (2003).
Darwin, C. On the Origin of Species by Means of Natural Selection (John Murray, Albemarle Street, London, 1859).
Sakarya, O. et al. A post-synaptic scaffold at the origin of the animal kingdom. PLoS ONE 2, e506 (2007). A detailed and careful study of 36 postsynaptic gene families in poriferans and cnidarians
Garcia, M. L. & Strehler, E. E. Plasma membrane calcium ATPases as critical regulators of calcium homeostasis during neuronal cell function. Front. Biosci. 4, D869–D882 (1999).
Muller, D., Buchs, P. A., Stoppini, L. & Boddeke, H. Long-term potentiation, protein kinase C, and glutamate receptors. Mol. Neurobiol. 5, 277–288 (1991).
Emes, R. D. et al. Evolutionary expansion and anatomical specialization of synapse proteome complexity. Nature Neurosci. 11, 799–806 (2008). The first study to combine comparative genomics and proteomics to address the origin and evolution of the PSD and MASC complexes
Miyakawa, T. et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc. Natl Acad. Sci. USA 100, 8987–8992 (2003).
Cyert, M. S. Genetic analysis of calmodulin and its targets in Saccharomyces cerevisiae. Annu. Rev. Genet. 35, 647–672 (2001).
King, N. Choanoflagellates. Curr. Biol. 15, R113–R114 (2005).
Ruiz-Trillo, I. et al. The origins of multicellularity: a multi-taxon genome initiative. Trends Genet. 23, 113–118 (2007).
King, N. The unicellular ancestry of animal development. Dev. Cell 7, 313–325 (2004). An informative review on the importance of choanoflagellate research to our knowledge of the evolution of multicellularity.
Leys, S. P., Rohksar, D. S. & Degnan, B. M. Sponges. Curr. Biol. 15, R114–R115 (2005).
King, N. & Carroll, S. B. A receptor tyrosine kinase from choanoflagellates: molecular insights into early animal evolution. Proc. Natl Acad. Sci. USA 98, 15032–15037 (2001).
King, N., Hittinger, C. T. & Carroll, S. B. Evolution of key cell signaling and adhesion protein families predates animal origins. Science 301, 361–363 (2003).
Pincus, D., Letunic, I., Bork, P. & Lim, W. A. Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages. Proc. Natl Acad. Sci. USA 105, 9680–9684 (2008).
Manning, G., Young, S. L., Miller, W. T. & Zhai, Y. The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan. Proc. Natl Acad. Sci. USA 105, 9674–9679 (2008).
Grant, S. G. et al. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science 258, 1903–1910 (1992).
Salter, M. W. & Kalia, L. V. Src kinases: a hub for NMDA receptor regulation. Nature Rev. Neurosci. 5, 317–328 (2004).
Abedin, M. & King, N. The premetazoan ancestry of cadherins. Science 319, 946–948 (2008).
Arikkath, J. & Reichardt, L. F. Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci. 31, 487–494 (2008).
Nichols, S. A., Dirks, W., Pearse, J. S. & King, N. Early evolution of animal cell signaling and adhesion genes. Proc. Natl Acad. Sci. USA 103, 12451–12456 (2006).
Jessell, T. M. & Sanes, J. R. Development. The decade of the developing brain. Curr. Opin. Neurobiol. 10, 599–611 (2000).
Leys, S. P. & Degnan, B. M. Cytological basis of photoresponsive behavior in a sponge larva. Biol. Bull. 201, 323–338 (2001).
Muller, W. E. Review: How was metazoan threshold crossed? The hypothetical Urmetazoa. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 129, 433–460 (2001).
Perovic, S., Krasko, A., Prokic, I., Muller, I. M. & Muller, W. E. Origin of neuronal-like receptors in Metazoa: cloning of a metabotropic glutamate/GABA-like receptor from the marine sponge Geodia cydonium. Cell Tissue Res. 296, 395–404 (1999).
Leys, S. P., Mackie, G. O. & Meech, R. W. Impulse conduction in a sponge. J. Exp. Biol. 202, 1139–1150 (1999).
Lin, C. H. et al. A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala. Neuron 31, 841–851 (2001).
Sweatt, J. D. Protooncogenes subserve memory formation in the adult CNS. Neuron 31, 671–674 (2001).
Elias, G. M. & Nicoll, R. A. Synaptic trafficking of glutamate receptors by MAGUK scaffolding proteins. Trends Cell Biol. 17, 343–352 (2007).
Kessels, H. W. & Malinow, R. Synaptic AMPA receptor plasticity and behavior. Neuron 61, 340–350 (2009).
Nakazawa, K., McHugh, T. J., Wilson, M. A. & Tonegawa, S. NMDA receptors, place cells and hippocampal spatial memory. Nature Rev. Neurosci. 5, 361–372 (2004).
Craig, A. M. & Kang, Y. Neurexin-neuroligin signaling in synapse development. Curr. Opin. Neurobiol. 17, 43–52 (2007).
Hedges, S. B., Dudley, J. & Kumar, S. TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22, 2971–2972 (2006).
De Robertis, E. M. Evo-devo: variations on ancestral themes. Cell 132, 185–195 (2008).
Sanchez-Soriano, N. et al. Are dendrites in Drosophila homologous to vertebrate dendrites? Dev. Biol. 288, 126–138 (2005).
Walker, R. J., Brooks, H. L. & Holden-Dye, L. Evolution and overview of classical transmitter molecules and their receptors. Parasitology 113, S3–S33 (1996).
Littleton, J. T. & Ganetzky, B. Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron 26, 35–43 (2000).
Naisbitt, S. et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23, 569–582 (1999).
Sheng, M. & Kim, E. The Shank family of scaffold proteins. J. Cell Sci. 113, 1851–1856 (2000).
Gerrow, K. et al. A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49, 547–562 (2006).
Ryan, T. J., Emes, R. D., Grant, S. G. & Komiyama, N. H. Evolution of NMDA receptor cytoplasmic interaction domains: implications for organisation of synaptic signalling complexes. BMC Neurosci. 9, 6 (2008). This paper identifies the deuterostome specific elongated NR2 intracellular domain and discusses it implications for NMDA receptor evolution
te Velthuis, A. J., Admiraal, J. F. & Bagowski, C. P. Molecular evolution of the MAGUK family in metazoan genomes. BMC Evol. Biol. 7, 129 (2007).
Sprengel, R. et al. Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 92, 279–289 (1998). This study establishes the indispensable role of the vertebrate NR2 intracellular carboxy-terminal domain in NMDA receptor function
McLysaght, A., Hokamp, K. & Wolfe, K. H. Extensive genomic duplication during early chordate evolution. Nature Genet. 31, 200–204 (2002).
Okamura, Y. et al. Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes. Physiol. Genomics 22, 269–282 (2005).
Cull-Candy, S., Brickley, S. & Farrant, M. NMDA receptor subunits: diversity, development and disease. Curr. Opin. Neurobiol. 11, 327–335 (2001).
Kim, M. J., Dunah, A. W., Wang, Y. T. & Sheng, M. Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron 46, 745–760 (2005).
Prybylowski, K. et al. The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron 47, 845–857 (2005).
Townsend, M., Liu, Y. & Constantine-Paton, M. Retina-driven dephosphorylation of the NR2A subunit correlates with faster NMDA receptor kinetics at developing retinocollicular synapses. J. Neurosci. 24, 11098–11107 (2004).
Li, B. S. et al. Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc. Natl Acad. Sci. USA 98, 12742–12747 (2001).
Sans, N. et al. A developmental change in NMDA receptor-associated proteins at hippocampal synapses. J. Neurosci. 20, 1260–1271 (2000).
Funke, L., Dakoji, S. & Bredt, D. S. Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu. Rev. Biochem. 74, 219–245 (2005).
Wang, D. et al. CD3/CD28 costimulation-induced NF-κB activation is mediated by recruitment of protein kinase C-τ, Bcl10, and IκB kinase β to the immunological synapse through CARMA1. Mol. Cell Biol. 24, 164–171 (2004).
Migaud, M. et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396, 433–439 (1998).
Cuthbert, P. C. et al. Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J. Neurosci. 27, 2673–2682 (2007).
Carlisle, H. J., Fink, A. E., Grant, S. G. & O'Dell, T. J. Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. J. Physiol. 586, 5885–5900 (2008).
Xia, S. et al. NMDA receptors mediate olfactory learning and memory in Drosophila. Curr. Biol. 15, 603–615 (2005). The first study to clearly demonstrate that NMDA receptors mediate learning in an invertebrate organism.
Martyniuk, C. J., Aris-Brosou, S., Drouin, G., Cahn, J. & Trudeau, V. L. Early evolution of ionotropic GABA receptors and selective regimes acting on the mammalian-specific τ and ɛ subunits. PLoS ONE 2, e894 (2007).
Tsang, S. Y., Ng, S. K., Xu, Z. & Xue, H. The evolution of GABAA receptor-like genes. Mol. Biol. Evol. 24, 599–610 (2007).
Simon, J., Wakimoto, H., Fujita, N., Lalande, M. & Barnard, E. A. Analysis of the set of GABA(A) receptor genes in the human genome. J. Biol. Chem. 279, 41422–41435 (2004).
Mitri, C., Parmentier, M. L., Pin, J. P., Bockaert, J. & Grau, Y. Divergent evolution in metabotropic glutamate receptors. A new receptor activated by an endogenous ligand different from glutamate in insects. J. Biol. Chem. 279, 9313–9320 (2004).
Dillon, J., Hopper, N. A., Holden-Dye, L. & O'Connor, V. Molecular characterization of the metabotropic glutamate receptor family in Caenorhabditis elegans. Biochem. Soc. Trans. 34, 942–948 (2006).
Yanay, C., Morpurgo, N. & Linial, M. Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle. Genome Biol. 9, R27 (2008).
Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Scharfe, C. & Feldman, M. W. Evolutionary rate in the protein interaction network. Science 296, 750–752 (2002).
Hadley, D. et al. Patterns of sequence conservation in presynaptic neural genes. Genome Biol. 7, R105 (2006).
Winter, E. E., Goodstadt, L. & Ponting, C. P. Elevated rates of protein secretion, evolution, and disease among tissue-specific genes. Genome Res. 14, 54–61 (2004).
Sugino, K. et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nature Neurosci. 9, 99–107 (2006).
Ohno, S. Evolution by gene duplication (Allen & Unwin, 1970).
Thompson, C. L. et al. Genomic anatomy of the hippocampus. Neuron 60, 1010–1021 (2008).
Heiman, M. et al. A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738–748 (2008).
Doyle, J. P. et al. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135, 749–762 (2008).
Varki, A., Geschwind, D. H. & Eichler, E. E. Explaining human uniqueness: genome interactions with environment, behaviour and culture. Nature Rev. Genet. 9, 749–763 (2008).
Mekel-Bobrov, N. & Lahn, B. T. What makes us human: revisiting an age-old question in the genomic era. J. Biomed. Discov. Collab. 1, 18 (2006).
Sikela, J. M. The jewels of our genome: the search for the genomic changes underlying the evolutionarily unique capacities of the human brain. PLoS Genet. 2, e80 (2006).
Gilbert, S. L., Dobyns, W. B. & Lahn, B. T. Genetic links between brain development and brain evolution. Nature Rev. Genet. 6, 581–590 (2005).
Dorus, S. et al. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119, 1027–1040 (2004).
Gardner, P. P. & Vinther, J. Mutation of miRNA target sequences during human evolution. Trends Genet. 24, 262–265 (2008).
Andres, A. M. et al. Positive selection in MAOA gene is human exclusive: determination of the putative amino acid change selected in the human lineage. Hum. Genet. 115, 377–386 (2004).
Caspi, A. et al. Role of genotype in the cycle of violence in maltreated children. Science 297, 851–854 (2002).
Buckholtz, J. W. & Meyer-Lindenberg, A. MAOA and the neurogenetic architecture of human aggression. Trends Neurosci. 31, 120–129 (2008).
Ding, Y. C. et al. Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc. Natl Acad. Sci. USA 99, 309–314 (2002).
Swanson, J. et al. Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc. Natl Acad. Sci. USA 97, 4754–4759 (2000).
Wang, E. et al. The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. Am. J. Hum. Genet. 74, 931–944 (2004).
Lo, W. S. et al. Association of SNPs and haplotypes in GABAA receptor β2 gene with schizophrenia. Mol. Psychiatry 9, 603–608 (2004).
Lo, W. S. et al. Positive selection within the Schizophrenia-associated GABA(A) receptor β2 gene. PLoS ONE 2, e462 (2007).
Zhao, C. et al. Two isoforms of GABA(A) receptor β2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia. Mol. Psychiatry 11, 1092–1105 (2006).
Crow, T. J. The 'big bang' theory of the origin of psychosis and the faculty of language. Schizophr Res. 102, 31–52 (2008).
Pearlson, G. D. & Folley, B. S. Schizophrenia, psychiatric genetics, and Darwinian psychiatry: an evolutionary framework. Schizophr Bull. 34, 722–733 (2008).
Nieoullon, A. & Coquerel, A. Dopamine: a key regulator to adapt action, emotion, motivation and cognition. Curr. Opin. Neurol. 16 (Suppl 2), 3–9 (2003).
Caceres, M. et al. Elevated gene expression levels distinguish human from non-human primate brains. Proc. Natl Acad. Sci. USA 100, 13030–13035 (2003).
Enard, W. et al. Intra- and interspecific variation in primate gene expression patterns. Science 296, 340–343 (2002).
Valor, L. M., Charlesworth, P., Humphreys, L., Anderson, C. N. & Grant, S. G. Network activity-independent coordinated gene expression program for synapse assembly. Proc. Natl Acad. Sci. USA 104, 4658–4663 (2007).
Mattson, M. P. & Bruce-Keller, A. J. Compartmentalization of signaling in neurons: evolution and deployment. J. Neurosci. Res. 58, 2–9 (1999).
Hedges, S. B. & Kumar, S. The Timetree of Life (Oxford University Press, Oxford, 2009).
Kohr, G. NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res. 326, 439–446 (2006).
Dechant, R. & Peter M. Nutrient signals driving cell growth. Curr. Opin. Cell Biol. 20, 678–687 (2008).
Park, J. I., Grant, C. M. & Dawes, I. W. The high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae is the major determinant of cAMP levels in stationary phase: involvement of different branches of the Ras-cyclic AMP pathway in stress responses. Biochem. Biophys. Res. Commun. 327, 311–319 (2005).
Kraus, P. R. & Heitman J. Coping with stress: calmodulin and calcineurin in model and pathogenic fungi. Biochem. Biophys. Res. Commun. 311, 1151–1157 (2003).
Zeitlinger, J. et al. Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Cell 113, 395–404 (2003).
Slessareva, J. E. & Dohlman H. G. G protein signaling in yeast: new components, new connections, new compartments. Science 314, 1412–1413 (2006).
Sato, T. K. Vam7p, a SNAP-25-like molecule, and Vam3p, a syntaxin homolog, function together in yeast vacuolar protein trafficking. Mol. Cell Biol. 18, 5308–5319 (1998).
Denis, V. & Cyert M. S. Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. J. Cell Biol. 156, 29–34 (2002).
Li, W. et al. Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation. J. Biol. Chem. 283, 15491–15501 (2008).
Cai, X. Unicellular Ca2+ signaling 'toolkit' at the origin of metazoa. Mol. Biol. Evol. 25, 1357–1361 (2008).
Baines, A. J. Evolution of spectrin function in cytoskeletal and membrane networks. Biochem. Soc. Trans. 37, 796–803 (2009).
Kosik, K. S. Exploring the early origins of the synapse by comparative genomics. Biol. Lett (2008).
Adell, T. et al. Evolution of metazoan cell junction proteins: the scaffold protein MAGI and the transmembrane receptor tetraspanin in the demosponge Suberites domuncula. J. Mol. Evol. 59, 41–50 (2004).
Nakazawa, K. et al. NMDA receptors, place cells and hippocampal spatial memory. Nature Rev. Neurosci. 5, 361–372 (2004).
Kessels, H. W. & Malinow, R. Synaptic AMPA receptor plasticity and behavior. Neuron 61, 340–350 (2009).
Jane, D. E. Kainate receptors: pharmacology, function and therapeutic potential. Neuropharmacology 56, 90–113 (2009).
Lee, J. et al. Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by slowpoke and shaker K+ channel mutations in Drosophila. Neuroscience 154, 1283–1296 (2008).
Calin-Jageman, I. et al. Erbin enhances voltage-dependent facilitation of Cav1.3 Ca2+ channels through relief of an autoinhibitory domain in the Cav1.3 α1 subunit. J. Neurosci. 27, 1374–1385 (2007).
Atasoy, D. et al. Deletion of CASK in mice is lethal and impairs synaptic function. Proc. Natl Acad. Sci. USA 104, 2525–2530 (2007).
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.
- Postsynaptic proteome
The complete set of proteins currently identified at the postsynaptic side of the synapse.
Membrane-associated guanylate kinase (MAGUK) proteins act as scaffolds for the clustering of receptors, ion channels and associated signalling proteins at postsynaptic sites.
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.
Homologous genes that separated due to a speciation event.
Those synaptic components that were present before the emergence of synapses and most likely contributed to their evolution.
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.
A group of organisms that serves as a reference group for determination of the evolutionary relationship between monophyletic groups of organisms.
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.
Phylum of multicellular animals (poriferans or sponges) that lack a nervous system.
Organism belonging to the primary class of Porifera. Demosponges account for ∼90% all sponge species.
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.
An evolutionary group consisting of a given single common ancestor and all of its descendants.
Animals belonging to the phylum Protostomia, an animal clade that includes the superphyla Ecdysozoa (arthropods and nematodes) and Lophotrochozoa.
Animals belonging to the superphylum Deuterostomia that includes the subphylum Vertebrata.
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.
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.
About this article
Cite this article
Ryan, T., Grant, S. The origin and evolution of synapses. Nat Rev Neurosci 10, 701–712 (2009). https://doi.org/10.1038/nrn2717
This article is cited by
Post-synaptic specialization of the neuromuscular junction: junctional folds formation, function, and disorders
Cell & Bioscience (2022)
Scientific Reports (2020)
Superior Synaptogenic Effect of Electrospun PLGA-PEG Nanofibers Versus PLGA Nanofibers on Human Neural SH-SY5Y Cells in a Three-Dimensional Culture System
Journal of Molecular Neuroscience (2020)
Co-expression of synaptic genes in the sponge Amphimedon queenslandica uncovers ancient neural submodules
Scientific Reports (2019)
BMC Cell Biology (2018)