Marine animals called comb jellies have nervous systems unlike those of any other known animal. Their neurons are oddly shaped and use chemicals not found in those of other animals.

“These neurons are quite unique,” says Pawel Burkhardt at the University of Bergen in Norway.

The comb jellies’ peculiar neurons may be an adaptation for their lifestyle and the way their bodies work.

They also add to the ongoing debate among evolutionary biologists about how the first animal brains evolved. In particular, there is controversy over whether brains evolved once in very early animals, or several times in different groups.

Comb jellies, or ctenophores, are one of the oldest animal groups – and the oldest group to have a nervous system. Though they look a bit like jellyfish, they have a distinct evolutionary history. Their name comes from the “combs” that run along the outsides of their bodies. Each comb is a row of tiny tentacles, which propel the comb jelly through the water.

Comb jellies don’t have a large central brain. Instead they have a thin net of neurons. “What was elusive so far was what is going on with the nervous system,” says Burkhardt. Neurons in other animals produce characteristic chemicals, in particular, small proteins called neuropeptides. But nobody had identified neuropeptides in comb jelly neurons.

Read more: First ever animals were made of jelly, not sponge

Burkhardt’s team studied a comb jelly called Mnemiopsis leidyi, whose genome had already been sequenced. The researchers used a machine-learning tool to predict 129 possible neuropeptides from the genome. They then grew M. leidyi in the lab, and identified 16 of these neuropeptides in their neurons. They were unlike those seen in any other animal.

“They took a big risk in taking this approach and I think it paid off,” says Leslie Babonis of Cornell University in New York.

In follow-up experiments, the team used the neuropeptides to label individual neurons and found that four of the chemicals had detectable effects on behaviour, changing the speed at which comb jellies swam.

Finally, the researchers obtained a 3-dimensional image of a neuron from the animal’s nerve net. They created it by taking thin slices of a comb jelly and scanning them with an electron microscope, before combining the resulting images.

Neurons have a central cell body with several tendrils called neurites. The comb jelly neuron had a sprawling array of neurites, but they had fused together at multiple points. This means it isn’t just the neurons collectively that form a net: individual neurons also look net-like. “It looks more like a spiderweb or a trampoline,” says Burkhardt. “I have not seen this in any other animal lineages.”

A comb jelly neuron like this was drawn by German zoologist Richard Hertwig in his 1880 book Über den Bau der Ctenophoren, but only now has Burkhardt’s team confirmed the observation.

It isn’t clear why comb jellies would have net-like neurons. Burkhardt says it may be because to move they must simultaneously activate all their combs, which are widely spaced – so the signal to move must be transmitted all over the body quickly.

Read more: We may finally have figured out which group of animals evolved first

The discovery may add to the discussions of how brains evolved. For decades it was assumed the first animals didn’t have neurons because they are absent in sponges – the ancestors of which may have been the first of the still-surviving animal groups to branch off from the animal evolutionary tree and begin evolving independently.

However, some biologists now believe the ancestors of comb jellies rather than sponges were the first to branch off from the animal evolutionary tree, consistent with the idea that neurons and brains evolved at least twice independently. The M. leidyi genome, published in 2013, suggested as much – but since then the argument has gone back and forth.

The idea that comb jellies came first is counter-intuitive because they are more complex than sponges, says Babonis.

“It’s hard for people to accept this relationship between perceived complexity and the evolutionary order of these animals,” she says. “But there are more and more data coming out.”

Burkhardt says we shouldn’t conflate the question of which group split first with the question of how many times neurons evolved. He points out that another group of animals called placozoans are known to have split after the comb jellies, and lack neurons.

“Even if ctenophores are second, they could still very likely have made their own nervous system,” says Burkhardt. “I think it’s too early to say if [neurons] independently evolved. But this paper clearly opens the door further.”

Reference: bioRxiv, DOI: 10.1101/2021.03.31.437758