Neurons, the specialized cells of the nervous system, are possibly probably the most complicated cell type ever to have evolved. In humans, these cells are able to processing and transmitting vast sums of data. But how such complicated cells first got here about stays a long-standing debate.

Now, scientists in Japan have revealed the sort of messenger -;molecules that carry signals from one cell to a different -;that likely functioned in probably the most ancestral nervous system.

The study, published eighth August in Nature Ecology and Evolution, also revealed key similarities between the nervous system of two early-diverging animal lineages – the lineage of jellyfish and anemones (also called cnidarians) and that of comb jellies (ctenophores), reigniting an earlier hypothesis that neurons only evolved once.

Despite their supposed simplicity, little or no is thought in regards to the nervous system of ancient animals. Out of the 4 animal lineages that branched off before the rise of more complex animals, only comb jellies (the primary ancient lineage to diverge) and cnidarians (the last ancient lineage to diverge) are known to own neurons. But the distinctiveness of the comb jellies nervous system in comparison with that seen in cnidarians and more complex animals, and the absence of neurons within the two lineages that diverged in between, led some scientists to hypothesize that neurons evolved twice.

But Professor Watanabe, who leads the Evolutionary Neurobiology Unit on the Okinawa Institute of Science and Technology (OIST), remained unconvinced.

Indeed, comb jellies lack a variety of neural proteins that we see in additional evolved animal lineages. But for me, a scarcity of those proteins is not enough evidence for 2 independent neuron origins.”

Hiroshi Watanabe, Professor, Evolutionary Neurobiology Unit, Okinawa Institute of Science and Technology

In his study, Prof. Watanabe focused on an ancient and diverse group of neural messengers. Called neuropeptides, these short peptide chains are first synthesized in neurons as a protracted peptide chain, before being cleaved by digestive enzymes into many short peptides. They’re the most important type of messenger present in cnidarians, and likewise play a job in neural communication in humans, and other complex animals.

Nevertheless, past research that has attempted to seek out similar neuropeptides in comb jellies has been unsuccessful. The essential problem, explained Prof. Watanabe, is that the mature short peptides are encoded by only short sequences of DNA, and mutate often in these ancient lineages, making DNA comparisons too difficult. While artificial intelligence has identified potential peptides, these haven’t yet been experimentally validated.

So, Prof. Watanabe’s research team approached the issue from a latest direction. They extracted peptides from sponges, cnidarians and comb jellies and used mass spectrometry to go looking for brief peptides. The team was capable of find 28 short peptides in cnidarians and comb jellies and determine their amino acid sequences.

Now knowing their structures, the researchers visualized the short peptides under a fluorescent microscope, allowing them to see which cells they were produced in in each cnidarians and comb jellies.

In comb jellies, they found that one sort of neuropeptide-expressing cell looked much like classic neurons, with thin projections called neurites extending out from the cell.

However the short peptides were also produced in a second sort of cell that lacked neurites. The researchers suspect these could possibly be an early version of neuroendocrine cells – cells which receive signals from neurons after which release signals, like hormones, to other organs within the body.

The researchers also compared what genes were expressed in cnidarian and comb jelly neurons. They found that in addition to having some short neuropeptides in common, each neurons also expressed the same array of other proteins essential for neuronal function.

“We already know that cnidarian peptide-expressing neurons are homologous to those seen in additional complex animals. Now, comb jelly neurons have also been found to have the same “genetic signature”, suggesting that these neurons share the identical evolutionary origin,” said Prof. Watanabe. “In other words, it’s most certainly that neurons only evolved once.”

This implies, added Prof. Watanabe, that peptide-expressing neurons are probably probably the most ancestral form, with chemical neurotransmitters arising later.
For Prof. Watanabe, these findings bring latest, exciting inquiries to the forefront of his research.

“If that is true, I’m most interested to know – where did the peptide-expressing neurons come from? And why did the ancestral animal have to evolve neurons? Now that now we have a clearer idea of what the earliest neurons looked like, research into their original function can begin.”

Source:

Okinawa Institute of Science and Technology Graduate University

Journal reference:

Hayakawa, E., et al. (2022) Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons. Nature Ecology & Evolution. doi.org/10.1038/s41559-022-01835-7.