Neurons, the specialized cells of the nervous system, are possibly the most complicated cell type to ever evolve. In humans, these cells are able to process and transmit vast amounts of information. But how such complicated cells came about in the first place remains a long-standing debate.
Now scientists in Japan have discovered the type of messengers – molecules that carry signals from one cell to another – that likely functioned in the ancestral nervous system.
The study, published August 8 in natural ecology and evolution, also revealed important similarities between the nervous systems of two early divergent animal lineages – the lineage of jellyfish and anemones (also called cnidarians) and that of comb jellyfish (ctenophores), reviving a previous hypothesis that neurons evolved only once.
Despite their supposed simplicity, very little is known about the nervous systems of ancient animals. Of the four animal lineages that branched before the advent of more complex animals, only comb jellyfish (the first diverging ancient lineage) and cnidarians (the last diverging ancient lineage) are known to possess neurons. But the uniqueness of the nervous system of comb jellies compared to that of cnidarians and more complex animals, and the absence of neurons in the two lineages that diverge between them, led some scientists to hypothesize that neurons evolved twice.
But Professor Watanabe, who heads the Department of Evolutionary Neurobiology at the Okinawa Institute of Science and Technology (OIST), wasn’t convinced.
“Indeed, comb jellies lack many neural proteins that we see in more evolved animal lines,” he said. “But to me, a lack of these proteins is not sufficient evidence for two independent origins of neurons.”
In his study, Prof. Watanabe focused on an ancient and diverse group of neurotransmitters. These short peptide chains, called neuropeptides, are first synthesized in neurons as a long peptide chain before being cleaved into many short peptides by digestive enzymes. They are the main messenger form of cnidarians and also play a role in neural communication in humans and other complex animals.
However, previous research attempting to find similar neuropeptides in honeycomb jellies was unsuccessful. The main problem, explained Prof Watanabe, is that the mature short peptides are only encoded by short DNA sequences and mutate frequently in these old lines, making DNA comparisons too difficult. Although artificial intelligence has identified potential peptides, these have not yet been experimentally validated.
So Prof. Watanabe’s research team approached the problem from a new direction. They extracted peptides from sponges, cnidarians and honeycomb jellyfish and used mass spectrometry to look for short peptides. The team was able to find 28 short peptides in cnidarians and comb jellyfish and determine their amino acid sequences.
Now that the researchers knew their structures, they visualized the short peptides under a fluorescence microscope, which allowed them to see in which cells they were produced in both cnidarians and comb jellyfish.
In honeycomb jellies, they found that one type of neuropeptide-expressing cell looked similar to classic neurons, with thin projections called neurites extending outside the cell.
But the short peptides were also produced in a second cell type that lacked neurites. The researchers suspect that this could be an early version of neuroendocrine cells – cells that receive signals from neurons and then send signals, like hormones, to other organs in the body.
The researchers also compared which genes were expressed in cnidarian and honeycomb neurons. They found that both neurons not only shared some short neuropeptides, but also expressed a similar set of other proteins essential for neuronal function.
“We already know that neurons expressing cnidarian peptides are homologous to those seen in more complex animals. Now it has also been found that comb jellyfish neurons share a similar ‘genetic signature’, suggesting these neurons share the same evolutionary origin,’ he told Prof Watanabe. “In other words, it’s very likely that neurons only evolved once.”
This means, added Prof Watanabe, that peptide-expressing neurons are probably the most prevalent form, with chemical neurotransmitters emerging later. For Prof. Watanabe, these findings bring new, exciting questions to the forefront of his research.
“If that’s true, what interests me most is knowing – where did the peptide-expressing neurons come from?” And why did the proto-animal need to evolve neurons? Now that we have a clearer idea of what the earliest neurons looked like, exploration of their original function can begin.”