Studies Have Found That Brain Signal Proteins Evolved Earlier Than Animals Themselves

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Our human brain seems to be the highest achievement of evolution, but the foundation of this achievement is very deep. The modern brain came into being with the gradual increase of complexity over hundreds of millions of years. Evolutionary biologists have traced this progress through the branches of the animal family tree, including all organisms with central nervous system, but it is clear that the basic elements of the nervous system have existed earlier.

The recent findings of a research team from the University of Exeter in the United Kingdom have made people have a clear understanding of how early. They found that chemical precursors of two important neurotransmitters (or signaling molecules used in the nervous system) appeared in all major animal populations, which existed before the central nervous system.

However, the biggest surprise is that these molecules also exist in animals' single-cell relatives, called flagellates. This discovery indicates that neuropeptides of animals have been originated even before the earliest animal evolution.

PAWEL Burkhardt, who studies the evolutionary origin of neurons at the International Marine Molecular Biology Center in SARS, Norway, said that this discovery "solves a long-term problem about when and how animal neuropeptides evolved". It also shows that at least some signal molecules that are crucial to the operation of our brain first evolved for a completely different purpose in organisms composed of only one cell.

The nervous system of animals is composed of interconnected neurons, which transmit information in synapses through various small peptide neurotransmitters. These peptides are the language that neurons talk to each other. This suggests that these neuronal molecules evolved even before such extensive cell-to-cell communication was required.

But when evolutionary biologists try to infer which animal cells first began to use this "language", the fuzziness of early animal evolution interferes with them. Almost all early animal groups produced molecules very similar to neuropeptides, including ctenophores (comb jellyfish) and cnidarians (jellyfish, corals and anemones). Even very simple animals called viviparous animals, which do not have neuron like cells, make neuropeptides. Sponges seem to be the only exception, which is why it is widely believed that animal neuropeptides originated from cnidarians or ctenophores after sponges branched out from other parts of the animal tree.

However, the problem with this theory is that the amino acid sequence of neuropeptides in early animal populations is very different from that of diploid animals. It seems that no neuropeptide has enough similarity to become their ancestor. To make matters worse, many unicellular animals, or protozoa, also produce a variety of unrelated neuropeptides. Clues to the evolution of neuropeptides in the brain seem to have disappeared.

Recently, Luis ya ñ EZ Guerra, who studies evolutionary neurobiology in the G á sp á R J é kely Laboratory of the University of Exeter, broke the deadlock. In order to trace the origin and evolution of neuropeptides in various animals, ya ñ EZ Guerra mapped neuropeptides to the evolutionary tree of early lineages and their close relatives, flagellates.

In his doctoral work, he has created a huge list of animal neuropeptides. When he began to look for these neuropeptides in animal trees, he accidentally realized that flagellates would produce protein precursors of two mature neuropeptides: Phoenix and nesfatin. This presence in flagellates is a surprise, because neuropeptides usually appear in the neurons of the sender and receiver. "In a single celled organism, this is even more difficult to make sense," said ya ñ EZ Guerra. "It shows that these neuronal molecules evolved even before they needed such extensive cell-cell communication. That's why it's a bit shocking.".

Neuropeptides have now been found in all major early branches of animal life, including (clockwise from the upper right corner) ctenophores or comb jellyfish, sponges, and cnidarians such as jellyfish and anemones.

The precursors of Phoenix and nesfatin are not directly used by the nervous system as neuropeptides; On the contrary, these long peptides are chemical precursors, which are cut and processed into smaller molecules to become functional and mature neuropeptides. Their hidden identity may be the reason why they are not identified as early promising clues.

Further search of gene expression data confirmed ya ñ EZ Guerra's premonition that Phoenix and nesfatin may be the key to understand the evolution of neuropeptides. Not only are precursor peptides present in flagellates, but they are also present in all early animal groups -- even spongioids, where they were neglected.

Given that the precursor molecules in flagellates are so directly related to these neuropeptides found in all animals, berkhardt explained: "the last common ancestor of all animals may have at least two neuropeptides."

The natural problem is. Since it can't be a neural signal, what do those neuropeptide precursors do in heteroflagellates? There is no clear answer yet. Flagellates do seem to produce mature phoenixin neuropeptides, but do not produce mature nesfatin neuropeptides. Flagellates may use their phoenixin neuropeptides to communicate with each other, for example, to coordinate the formation of flagellate communities.

But in their paper, ya ñ EZ Guerra and his colleagues also suggested that these precursors may be multifunctional molecules. They pointed out that according to their peptide sequences, both precursors may be secretory molecules. They also pointed out that although the Phoenix element precursor can be processed into neuropeptides, one of its segments can also become a "companion" to ensure that the protein is folded correctly, forming a key complex related to the mitochondrial energy collection device.

During the evolution of precursors, the selective pressure on these "part-time" functions may be greater than the need for any intercellular signal. At present, ya ñ EZ Guerra and Burkhardt are cooperating to study a mutant flagellate lacking Phoenix precursor to better understand its function. They are also looking for receptor molecules in flagellates that can accept neuropeptides.

Unfortunately, the fact that these two neuropeptide precursors are shared by all animals makes it difficult to simplify the early evolution of the nervous system. In December last year, Maria sachkova and her colleagues at the sass center cooperated with Burkhardt and reported that with the help of a machine learning tool, they had identified many strange neuropeptides encoded in the ctenophore genome, many of which were different from any other neuropeptides in the animal kingdom.

Neuropeptides are not the only unique feature of the ctenophore nervous system. Their neural network structure is so unusual that researchers suspect that they evolved independently of the nervous systems of humans and other animals. Why ctenophores do things in different ways is a mystery, but it is clear that the nervous system experienced a huge period of experiment and innovation in its early evolution - and at least some of these experiments began before the emergence of animals.

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