A Post-Synaptic Scaffold at the Origin of the Animal Kingdom

Abstract

BackgroundThe evolution of complex sub-cellular structures such as the synapse requires the assembly of multiple proteins, each conferring added functionality to the integrated structure. Tracking the early evolution of synapses has not been possible without genomic information from the earliest branching animals. As the closest extant relatives to the Eumetazoa, Porifera (sponges) represent a pivotal group for understanding the evolution of nervous systems, because sponges lack neurons with clearly recognizable synapses, in contrast to eumetazoan animals.Methodology/Principal FindingsWe show that the genome of the demosponge Amphimedon queenslandica possesses a nearly complete set of post-synaptic protein homologs whose conserved interaction motifs suggest assembly into a complex structure. In the critical synaptic scaffold gene, dlg, residues that make hydrogen bonds and van der Waals interactions with the PDZ ligand are 100% conserved between sponge and human, as is the motif organization of the scaffolds. Expression in Amphimedon of multiple post-synaptic gene homologs in larval flask cells further supports the existence of an assembled structure. Among the few post-synaptic genes absent from Amphimedon, but present in Eumetazoa, are receptor genes including the entire ionotropic glutamate receptor family.Conclusions/SignificanceHighly conserved protein interaction motifs and co-expression in sponges of multiple proteins whose homologs interact in eumetazoan synapses indicate that a complex protein scaffold was present at the origin of animals, perhaps predating nervous systems. A relatively small number of crucial innovations to this pre-existing structure may represent the founding changes that led to a post-synaptic element.

The origin and evolution of synaptic proteins – choanoflagellates lead the way

“…2B), thus having an earlier origin than previously described. Moreover, in agreement with previous studies (Alié and Manuel, 2010;Emes and Grant, 2012;Sakarya et al, 2007;Suga et al, 2013), most synaptic proteins evolved before the origin of synapses and are probably pleiotropic. Only a few synaptic proteins seem to be restricted to metazoans with synapses and some of them are indeed dedicated to synapse formation (e.g.…”

“…2B) (Sakarya et al, 2007;Ryan and Grant, 2009;Alié and Manuel, 2010). Those few synaptic proteins that have homologs in fungi and non-opisthokonts, such as SNAREs, Sec1/Munc18 (SM) and tomosyn, primarily function in the highly conserved process of exocytosis.…”

“…Choanoflagellates do not produce synapses and neurons, but the genome of M. brevicollis encodes synaptic protein homologs, including cation channels similar to voltage-gated sodium channels (Liebeskind et al, 2011;Gur Barzilai et al, 2012) and the postsynaptic density (PSD) proteins Homer, Shank and PSD-95 (Alié and Manuel, 2010;Emes and Grant, 2012;Ryan and Grant, 2009;Sakarya et al, 2007). Moreover, homologs of various types of metazoan plasma membrane Ca 2+ channels including the storeoperated channel, ligand-operated channels, voltage-operated channels, second messenger-operated channels and transient…”

Mutations in Nature Conferred a High Affinity Phosphatidylinositol 4,5-Bisphosphate-binding Site in Vertebrate Inwardly Rectifying Potassium Channels

“…Sponges are an important comparative group for understanding the relationships between extant unicellular protists and the first multicellular organisms from which all animals evolved (14,(17)(18)(19)(20). By studying the physiological and structural impact of "nature's mutations," we provide a window into the functional consequences of evolution that is represented in distantly related animal species.…”

A history of Evo-Devo research in Spain

“…First, the diploblastic (bearing only ectoderm and endoderm) and radial (no dorsal-ventral axis) cnidarians bear most of genes expressed in the mesoderm and in the D-V axis of bilaterians (Martindale et al, 2004;Matus et al, 2006); conversely, although cnidarians possess several different kinds of 'eyes' do not possess "the eye gene" Pax6 . Second, Porifera (sponges) lack organs and nervous system but possess a nearly complete set of post-synaptic proteins homologs that assemble into a complex structure (Sakarya et al, 2007). Therefore, there are no such things as "mesodermal", "eye", "segmentation", or "limb" genes; what we have are just molecules that bind to DNA, interact with each other, form multimeric complexes, etc.…”