Synapse Evolution
Press Release from Genes to Cognition on Brain Evolution. June 2008
Origins of the brain: Complex synapses drove brain evolution
The study shows that two waves of increased sophistication in the structure of nerve junctions could have been the force that allowed complex brains - including our own - to evolve. The big building blocks evolved before big brains.
Animal evolution has generated a wide range of species including single-celled animals and multicellular animals including invertebrates and vertebrates (left column, indicating time since common ancestor with humans). All of these animals show behavioural responses to their environment with vertebrates showing the most complex behaviours. Only the multicellular animals having anatomically specialised nerve cells forming their brains.
The synapses that form the junctions between nerve cells are made of many proteins organised together into 'molecular signal processors' (middle column, Synapse protein complexity). In vertebrates and invertebrates, these proteins control psychological functions including learning and memory.
Surprisingly, these synapse molecules exist in single-celled animals as a simple set of proteins (where they control response to environment), and this set was built upon to form a larger set used in the brains of invertebrates. This invertebrate set was expanded further in the brains of vertebrate species. The correlation between numbers of nerve cells in the brain of animals and the number of synaptic proteins shows that both contribute to the differences in species (right column).
Brainpower May Lie in Complexity of Synapses New York Times article by Nicholas Wade (6/10/08 )
Dr. Grant and colleagues reported online Sunday in Nature Neuroscience. In worms and flies, the synapses mediate simple forms of learning, but in higher animals they are built from a much richer array of protein components and conduct complex learning and pattern recognition, Dr. Grant said.
The finding may open a new window into how the brain operates. “One of the biggest questions in neuroscience is to answer what are the design principles by which the human brain is constructed, and this is one of those principles,” Dr. Grant said.
If the synapses are thought of as the chips in a computer, then brainpower is shaped by the sophistication of each chip, as well as by their numbers. “From the evolutionary perspective, the big brains of vertebrates not only have more synapses and neurons, but each of these synapses is more powerful — vertebrates have big Internets with big computers and invertebrates have small Internets with small computers,” Dr. Grant said.
He included yeast cells in his cross-species survey and found that they contain many proteins equivalent to those in human synapses, even though yeast is a single-celled microbe with no nervous system. The yeast proteins, used for sensing changes in the environment, suggest that the origin of the nervous system, or at least of synapses, began in this way.
The computing capabilities of the human brain may lie not so much in its neuronal network as in the complex calculations that its synapses perform, Dr. Grant said. Vertebrate synapses have about 1,000 different proteins, assembled into 13 molecular machines, one of which is built from 183 different proteins.
These synapses are not standard throughout the brain, Dr. Grant’s group has found; each region uses different combinations of the 1,000 proteins to fashion its own custom-made synapses.
Each synapse can presumably make sophisticated calculations based on messages reaching it from other neurons. The human brain has about 100 billion neurons, interconnected at 100 trillion synapses.
The roots of several mental disorders lie in defects in the synaptic proteins, more than 50 of which have been linked to diseases like schizophrenia, Dr. Grant said.
Dr. Edward Ziff, a synapse expert at New York University, said Dr. Grant’s work was the first in which synapses had been analyzed from a cross-species perspective. “I would say this work is unique,” he said. “Grant’s been a leader in making this type of analysis and he deserves a lot of credit for it, although a certain amount of guesswork is involved.”
Brain Science Podcast #51: Seth Grant on Synapse Evolution Play Episode 51
In this interview with Dr. Seth Grant from
First, he has discovered that some proteins associated with neuron signaling are actually found in primitive unicellular organisms like yeast.
He has also discovered that the protein structure of the synapse becomes more complex as one moves from invertebrates like fruit flies to vertebrates like mice, but that most of the complexity seems to have arisen early on in vertebrates.
Blog posts and other links:
Press Release from Genes to Cognition on Brain Evolution. June 2008
New York Times article by Nicholas Wade (
“Synapse Proteomics,” by Diane Jacobs. June 2008
“Synapse Proteomics & Brain Evolution.” Neurophilosophy blog. June 2008
“Increasing complexity of nerve synapses during evolution.” Deric Bownds. June 2008
Learn more about Dr. Grant’s work:
Genes to Cognitions (G2C) website
According to Dr. Grant:
The origins of the brain appear to be in a protosynapse or ancient set of proteins found in unicellular animals, and when unicellular animals evolved into metazoans or multicellular animals their protosynaptic architecture was coopted and embelished by the addition of new proteins onto that ancient protosynaptic set, and that set of new molecules was inserted into the junctions of the first neurons or the synapse between the first neurons in simple invertebrate animals. When invertebrates evolved into vertebrates, around a billion years ago, there was a further addition or enhancement of the number of these synaptic molecules and that has been conserved throughout vertebrate evolution where they have much larger numbers of synaptic molecules. The large complex synapses evolved before large anatomically complex brains.
The discovery that there are significant differences between the synapses in vertebrates and non-vertebrates is significant because it has long been assumed that synapses were essentially identical between species and that brain and behavioral complexity was based on having more neurons and bigger brains. Instead, Dr. Grant proposes an alternative hypothesis:
The first part of the brain to ever evolve was the protosynapse. In other words, synapses came first.
When this big synapse evolved what the vertebrate brain then did as it grew bigger and evolved afterwards; it exploited the new proteins that had evolved into making new types of neurons in new types of regions of the brain. In other words, we would like to put forward the view that the synapse evolution has allowed brain specialization, regionalization, to occur.
Complex Synapses Drive Evolution Of The Human Brain
Current thinking suggests that the protein components of nerve connections - called synapses - are similar in most animals from humble worms to humans and that it is increase in the number of synapses in larger animals that allows more sophisticated thought.
"Our simple view that 'more nerves' is sufficient to explain 'more brain power' is simply not supported by our study," explained Professor Seth Grant, Head of the Genes to Cognition Programme at the Wellcome Trust Sanger Institute and leader of the project.
"Although many studies have looked at the number of neurons, none has looked at the molecular composition of neuron connections. We found dramatic differences in the numbers of proteins in the neuron connections between different species".
"We studied around 600 proteins that are found in mammalian synapses and were surprised to find that only 50 percent of these are also found in invertebrate synapses, and about 25 percent are in single-cell animals, which obviously don't have a brain."
Synapses are the junctions between nerves where electrical signals from one cell are transferred through a series of biochemical switches to the next. However, synapses are not simply soldered joints, but mini-processors that give the nervous systems the property of learning and memory.
Remarkably, the study shows that some of the proteins involved in synapse signalling and learning and memory are found in yeast, where they act to respond to signals from their environment, such as stress due to limited food or temperature change.
"The set of proteins found in single-cell animals represents the ancient or 'protosynapse' involved with simple behaviours," continues Professor Grant. "This set of proteins was embellished by addition of new proteins with the evolution of invertebrates and vertebrates and this has contributed to the more complex behaviours of these animals.
"The number and complexity of proteins in the synapse first exploded when muticellular animals emerged, some billion years ago. A second wave occurred with the appearance of vertebrates, perhaps 500 million years ago".
One of the team's major achievements was to isolate, for the first time, the synapse proteins from brains of flies, which confirmed that invertebrates have a simpler set of proteins than vertebrates.
Most important for understanding of human thought, they found the expansion in proteins that occurred in vertebrates provided a pool of proteins that were used for making different parts of the brain into the specialised regions such as cortex, cerebellum and spinal cord.
Since the evolution of molecularly complex, 'big' synapses occurred before the emergence of large brains, it may be that these molecular evolutionary events were necessary to allow evolution of big brains found in humans, primates and other vertebrates.
Behavioral studies in animals in which mutations have disrupted synapse genes support the conclusion that the synapse proteins that evolved in vertebrates give rise to a wider range of behaviours including those involved with the highest mental functions. For example, one of the 'vertebrate innovation' genes called SAP102 is necessary for a mouse to use the correct learning strategy when solving mazes, and when this gene is defective in human it results in a form of mental disability.
"The molecular evolution of the synapse is like the evolution of computer chips - the increasing complexity has given them more power and those animals with the most powerful chips can do the most," continues Professor Grant.
Simple invertebrate species have a set of simple forms of learning powered by molecularly simple synapses, and the complex mammalian species show a wider range of types of learning powered by molecularly very complex synapses.
"It is amazing how a process of Darwinian evolution by tinkering and improvement has generated, from a collection of sensory proteins in yeast, the complex synapse of mammals associated with learning and cognition," said Dr. Richard Emes, Lecturer in Bioinformatics at Keele University (UK), and joint first author on the paper.
The new findings will be important in understanding normal functioning of the human brain and will be directly relevant to disease studies. Professor Grant's team have identified recently evolved genes involved in impaired human cognition and modelled those deficits in the mouse.
"This work leads to a new and simple model for understanding the origins and diversity of brains and behaviour in all species" says Professor Grant, adding that "we are one step closer to understanding the logic behind the complexity of human brains".
This research was a collaboration between scientists in the Wellcome Trust Sanger Institute, Edinburgh University and Keele University (UK).
References:
“Proteomic analysis of NMDA receptor-adhesion protein signaling complexes.” Nature Neuroscience 2000 Jul;3(7):661-9. Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG.
“Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases.” Human Molecular Genetics 2005 Oct 15;14 Spec No. 2:R225-34. Grant SG, Marshall MC, Page KL, Cumiskey MA, Armstrong JD.
“The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour.” Molecular Systems Biology 2: 2006.0023. Pocklington AJ, Cumiskey M, Armstrong JD, Grant SG.
2008 “Evolutionary expansion and anatomical specialization of synapse proteome complexity.” Nature Neuroscience 2008. Emes RD, Pocklington AJ, Anderson CN, Bayes A, Collins MO, Vickers CA, Croning MD, Malik BR, Choudhary JS, Armstrong JD, Grant SG
Abstract
Understanding the origins and evolution of synapses may provide insight into species diversity and the organization of the brain. Using comparative proteomics and genomics, we examined the evolution of the postsynaptic density (PSD) and membrane-associated guanylate kinase (MAGUK) membrane-associated signaling complexes (MASCs) that underlie learning and memory. PSD and MASC orthologs found in yeast carry out basic cellular functions to regulate protein synthesis and structural plasticity. We observed marked changes in signaling complexity at the yeast-metazoan and invertebrate-vertebrate boundaries, with an expansion of key synaptic components, notably receptors, adhesion / cytoskeletal proteins and scaffold proteins. A proteomic comparison of Drosophila and mouse MASCs revealed species-specific adaptation with greater signaling complexity in mouse. Although synaptic components were conserved amongst diverse vertebrate species, mapping mRNA and protein expression in the mouse brain showed that vertebrate-specific components preferentially contributed to differences between brain regions. We propose that the evolution of synapse complexity around a core proto-synapse has contributed to invertebrate-vertebrate differences and to brain specialization.
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