Neurosciences Brain Evolution
HC 7
The origin and evolution of synapses
Synapses are the key functional components of a nervous system, enabling information
exchange between cells in a multicellular organism. The exact information exchange is
mediated by neurons, which receive and send on information via the contact points, also
known as synapses. All neurons, with their axons and dendrites, and synapses together form
an information network which together process complex information. Information, in fact,
exists of electrical signals or action potentials.
The synapse itself has a pre- and postsynaptic element, in between there is a synaptic cleft
wherein neurotransmitters are released or where gap junctions are located to propagate
and transduce signals. Synapses arose, in the course of evolution, already in unicellular
organisms. Not the exact mechanism was apparent, but the fundament for the molecular
machinery, the protosynapse, has been found before the evolution of metazoans and
neurons.
Ryan and Grant carried out proteomic and genomic research into the synapse, finding out
the hierarchy and the gradual transition of protosynapse, into ursynapse and the synapse
we know nowadays. Proteomic and genomic research coupled with molecular phylogenetic
approaches gave new insights into identification and adaptation which mediated
diversification and natural selection of synapses between species. Proteomics provided the
protein constituents of synapses and their interactions. These studies, for example, helped
determine the postsynaptic density (PSD) which consists of ion channels, multiprotein
complexes associated with neurotransmitter receptors, cell adhesion molecules, etc.
Comparative genomics was used to examine the origin and diversity of synaptic proteins,
especially the relationship between species. Together, thus, they provide opportunities to
map the evolution of synapses across species.
The last common ancestor of all synapses, the ursynapse, gives insights into the how and
why of the origin of the first synapse. One must identify the minimal and ancestral
components. The composition of the ursynapse was determined by taking synaptic proteins
and searching for orthologs in two categories of species. Orthologs are genes or proteins
that have the same function/structure in different organisms. The two categories:
- Unicellular eukaryotes + multicellular metazoans, these lack a nervous system, so
show synaptic components before the nervous system existed. These proteins make
up the protosynapse.
- Non-bilaterian multicellular metazoans that have a nervous system, which show
synaptic components in primitive synapses. These thus give insight into the
composition of the synapse shortly after it originated.
Protosynaptic organisms, so those of the first category, features synaptic protein families
still conserved in yeast and the amoeba. Some of the proteins here, which are thus also
present in today’s synapses, are PMCA (plasma membrane calcium ATPase) and PKC
(protein kinase C). It actually turns out 25% of PSD genes were orthologues in protosynaptic
organisms. Loss of function of these genes in yeast, showed impaired response to
environmental changes, like vesicular trafficking and cytoskeletal regulation. Essential
players that mediate neuronal changes during synaptic plasticity are also present in yeast,
, like the membrane proteins regulating calcium influx, which are implicated in postsynaptic
signaling pathways in neurons and in environmental responses in yeast.
Organisms more closely related to metazoans, so easier to study the origin of the synapse,
are the choanoflagellates. Though they are unicellular, they are the closest relative to the
multicellular metazoans based on cell body structure and nuclear/mitochondrial DNA. It
appears choanoflagellates have several synaptic molecules absent in other non-metazoans,
like the tyrosine kinases. They actually form an apparatus already, which now is known to
play a key role in plasticity at excitatory synapses. Choanoflagellates, furthermore, feature
cadherins which are needed in excitatory synaptogenesis. Cadherin is important in
choanoflagellates for cytoskeletal rearrangement and presents a precursor here
(interactions between multiple proteins would be homophilic first, later heterophilic). When
assessing the sponge, various comparative genomics studies have identified genes that
possibly played a role in the formation of synaptic junctions and synaptogenesis. The
molecules these genes encode though, emerged before the evolution of synapses, in an
ancestor common to choanoflagellates and metazoans. There are several more proteins
that are strongly conserved between sponges and Bilateria, suggesting they form a
protosynaptic complex that represents the precursor to synaptic sites. The sponge,
furthermore, expresses important ion channels and receptors present in today’s synapses,
like the metabotropic glutamate receptor, GABA receptors and neurexin. There are no
excitatory, ionotropic glutamate receptors, but there are in turn inhibitory, ionotropic GABA
receptors – the former hence evolved later than the latter.
All of the above implies there is a co-localized protosynaptic complex expressed in an
anatomical region active in environmental adaptation, which emerged at the same time as
the first synaptic channels and receptors. These proteins are pleiotropic, being active in
intracellular signaling as well, but evolved a discrete synaptic function, nevertheless.
Protosynaptic proteins are thus a pre-adaptation later co-opted for synaptic function and
which may have contributed to the first synapse.
The second category, primitive metazoans, exhibit visible synapses and feature a
rudimentary nervous system. Organisms here are cnidarians that branch off from bilaterians
which thus have a common ancestor that featured an original synapse. The most notable
feature of cnidarians is the emergence of postsynaptic ionotropic glutamate receptors like
AMPA and NMDA. In addition, a common ancestor of cnidarians has the transmembrane
neuroligin protein, which interacts with neurexin. The interaction plays a role in both
inhibitory and excitatory synapses; non-neuronal cells expressing the two even differentiate
into synapses. Further emerging structures, like ion channels, plug into pre-existing
protosynaptic intracellular scaffolding proteins (of which neurexin also was one, so the
emergence of neuroligin kicked off a new chapter).
When comparing vertebrates with invertebrates, a certain degree of divergence has
occurred. Of the Bilaterians, there are two major clades; protostomes and deuterostomes.
The former includes the invertebrates, while the latter has the vertebrates. Their last
common ancestor, the urbilaterian, gave rise to the vast majority of animal diversity we
know now. Comparing proto- and deuterostomes, commonalities indicate features of the
urbilaterian, while differences show features that have evolved specifically in each clade.
Comparing synapses, there are various differences, like the fact that dendrites can develop
from both the primary neurite (axons) and cell body in invertebrates, while in vertebrates
