The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans

Abstract

Background: Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals) and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans) offer an opportunity to refine our understanding of post-synaptic protein evolution.

Results: Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG) and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage.

Conclusions: The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving synapse through the addition of novel functionalities.

Figure 1

Summary of the occurrence of post-synaptic proteins in the investigated genomes. Yellow fields indicate presence of an orthologue as determined from the corresponding gene tree topology. Letters correspond to the three additional confidence criteria for orthology assignments defined in the Methods section: b, ML bootstrap value >= 70% and/or Bayesian posterior probability >= 0.95; c, congruence between at least two partitions of the same protein or between different domains; d, conservation of domain architecture. Note that Homo and Drosophila have been used as reference taxa for defining the orthology groups.

Figure 2

Gains (coloured dashes) and losses (ellipses) of post-synaptic proteins reconstructed onto the taxon phylogeny under the parsimony criterion. Placozoans are here placed as the sister-group to other metazoans. The total number of gains + losses is 45 (see less parsimonious reconstructions obtained for alternative placements of placozoans in Additional file 6). Events are labelled in bold when the corresponding gene orthology is supported by at least two confidence criteria in addition to gene tree topology (see explanations in Methods); otherwise they are labelled in normal font.

Figure 3

Graphic representation of the mammalian post-synaptic density, with the origination period of the genes indicated by the same colours as in Fig. 2. Domain structures are represented only for scaffold proteins. For most PDZ-binding proteins, the PDZ ligand has been labelled in grey, because the extent of sequence variability observed among PDZ ligands across taxa and proteins is so high that it is generally impossible to conclude either for or against the presence of a PDZ ligand (except for CRIPT and δ-cat; see Additional file 4). A darker red colour has been used for the Shank SAM domain, as it might not have been present in the Shank protein of the common choanoflagellate-metazoan ancestor (see text). Note that the general configuration of the post-synaptic scaffold has been completely re-drawn with respect to [2] (their Fig. 1), to account for data available in the recent literature (e.g. [17,18]).