Our human brains can seem like a crowning achievement of evolution, but the roots of that achievement run deep: The modern brain arose from hundreds of millions of years of incremental advances in complexity. Evolutionary biologists have traced that progress back through the branch of the animal family tree that includes all creatures with central nervous systems, the bilaterians, but it is clear that fundamental elements of the nervous system existed much earlier.

How much earlier has now been made dramatically clear by a recent discovery by a team of researchers at the University of Exeter in the United Kingdom. They found that the chemical precursors of two important neurotransmitters, or signaling molecules used in nervous systems, appear in all the major animal groups that preceded creatures with central nervous systems.

The big surprise, however, is that these molecules are also present in single-celled relatives of animals, called choanoflagellates. This finding shows that animal neuropeptides originated before the evolution of even the very first animals.

The discovery “solves a long-standing question about when and how animal neuropeptides evolved,” said Pawel Burkhardt, who studies the evolutionary origin of neurons at the Sars International Center for Marine Molecular Biology in Norway. It also indicates that at least some of the signaling molecules fundamental to the operation of our brains first evolved for an entirely different purpose in organisms that consisted of only a single cell.

Animal nervous systems are made of neurons that connect to each other, zipping information across synapses with a variety of small peptide neurotransmitters. These peptides are the language with which neurons speak to each other.

But when evolutionary biologists tried to deduce which animal cells first started to use that language, the murkiness of early animal evolution interfered. A variety of molecules very similar to neuropeptides are made by nearly all the early animal groups, including the ctenophores (comb jellies) and the cnidaria (jellyfish, corals and sea anemones). Even the extremely simple animals called placozoans, which have no cells resembling neurons, make neuropeptides. Sponges seemed to be the only exception, which is why it was generally thought that animal neuropeptides originated in cnidarians or ctenophores, after sponges branched away from the rest of the animal tree.

The problem with that theory, though, is that the amino acid sequences of the neuropeptides in the early animal groups are so different from bilaterian neuropeptides that none seemed similar enough to be ancestral to them. Worse, a wide variety of unrelated neuropeptides are also made by many single-celled animals, or protozoans. The evolutionary trail for brain neuropeptides seemed to vanish into a thicket.

This impasse was broken recently by Luis Yañez-Guerra, who studies evolutionary neurobiology in the lab of Gáspár Jékely at the University of Exeter. To trace the origin and evolution of various animal neuropeptides, Yañez-Guerra mapped neuropeptides onto the evolutionary tree of early-branching animals and their close relatives, the choanoflagellates.

From his doctoral work, he had already created a large list of animal neuropeptides, and as he began looking for them farther down the animal tree, he stumbled on the realization that choanoflagellates made protein precursors of two mature neuropeptides, phoenixin and nesfatin.

Their presence in choanoflagellates was a surprise because neuropeptides typically appear in the context of sender and receiver neurons. “In a unicellular organism, it’s more difficult to make sense of,” Yañez-Guerra said. “This shows that these neuronal molecules started evolving even before the need for this extensive communication between cell and cell. That’s why it was kind of shocking.”