Animals with sophisticated neurological systems, such as cephalopods like octopus, squid, and cuttlefish, are extremely intelligent. In “Science Advances”, a team from the Max Delbrück Center led by Nikolaus Rajewsky demonstrated that their development is linked to a huge increase in the number of microRNAs they have.
If we go far enough back in evolution, we will find the last common ancestor of humans and cephalopods: a basic worm-like creature with limited intellect and rudimentary eye spots. In the end, the entire animal world can be roughly broken down into two categories: vertebrates and invertebrates.
Invertebrates, unlike their vertebrate counterparts, have not developed massive, sophisticated brains capable of a wide range of cognitive abilities. This was particularly the case with primates and other mammals.
For a very long time, researchers wondered why only these molluscs were able to build such a sophisticated neural system. Now an international group led by scientists from the Max Delbrück Center and Dartmouth College in the United States has offered an explanation. They describe how octopuses have a much larger repertoire of microRNAs (miRNAs) in their brain tissue, matching comparable advances that have occurred in vertebrates, in a paper published in “Science Advances”. Professor Nikolaus Rajewsky, final author of the paper and head of the Systems Biology Laboratory of Gene Regulatory Elements at the Berlin Institute for Medical Systems Biology (MDC-BIMSB), exclaimed: “This is so what binds us to the octopus! His research suggests that miRNAs play a crucial role in shaping sophisticated brains, he says.
Rajewsky read a book in 2019 describing the genetic analysis of octopuses. The researchers found evidence that these cephalopods engage in a significant amount of RNA editing, indicating that they make considerable use of certain enzymes capable of recoding their RNA. This made Rajewsky wonder if octopuses had any other RNA tricks up their sleeves besides being skilled editors. So he started working with the marine research station Stazione Zoologica Anton Dohrn in Naples. The station sent him samples of 18 different types of dead octopus tissue.
According to Rajewsky, the results of this analysis were unexpected: “There was indeed a lot of RNA editing going on, but not in the areas that we think are interesting.” In fact, the most fascinating discovery was the significant increase in the number of a well-known collection of RNA genes called microRNAs. Forty-two new families of miRNAs have been identified, almost entirely within the brain and other nervous tissues. The team thinks these genes must have been functionally significant for cephalopods to have been conserved throughout their evolution.
Rajewsky has spent more than 20 years studying miRNAs. These genes code for short RNA fragments that bind to messenger RNA and regulate protein synthesis instead of being translated into messenger RNAs that carry the instructions for protein synthesis in the cell. These binding sites also remained the same during cephalopod evolution, which is another sign that these new miRNAs are important for function.
New families of microRNAs
“This is the third largest expansion of microRNA families in the animal world, and the largest outside of vertebrates,” adds lead author Grygoriy Zolotarov. “To give you an idea of the scale, oysters, which are also molluscs, have only acquired five new microRNA families since the last ancestors they shared with octopuses – while octopuses have acquired 90!
Zolotarov continues that oysters aren’t exactly famous for their intellect.
Years ago, during an evening visit to the Monterey Bay Aquarium in California, Rajewsky developed a fascination with octopuses.
“I saw this creature sitting at the bottom of the tank and we spent several minutes – or so I thought – staring at each other.”
The octopus, he says, is very different from the fish: “It’s not very scientific, but their eyes give off a sense of intelligence.”
Octopuses have sophisticated “camera” eyes like humans.
Octopuses are distinguished from other invertebrates by their distinct evolutionary history. They possess a central nervous system and a peripheral nervous system, the latter being capable of autonomous action. Even if an octopus loses one of its tentacles, the remaining tentacle is still mobile and sensitive to touch. The fact that octopuses use their arms in extremely specific ways, like tools for opening shells, may be why they are the only animal species to have developed such complex brain functions. Octopuses exhibit additional intelligence in the form of curiosity and memory. They can also tell who people are, and some of them they like more than others. Researchers now believe they even dream because their skin and color change while they sleep.
Rajewsky quotes the saying: “They say if you want to meet an alien, go dive and make friends with an octopus.”
Now he wants to build a European network of octopus researchers to facilitate more communication and collaboration in their fields. Although there is not yet a large group of octopus researchers, Rajewsky says interest in octopuses is spreading across the world. He finds it fascinating to study a kind of intellect that has developed independently. But it’s hard: “If you experiment with them using small snacks as a reward, they quickly lose interest. At least that’s what my colleagues tell me,” adds Rajewsky.
Since octopuses are not typical model organisms, our molecular biology tools were very limited,” says Zolotarov. “So we don’t yet know exactly which cell types are expressing the new microRNAs.”
Currently, Rajewsky’s team is preparing to use a method that was created in his lab to make octopus tissue cells visible at the molecular level.
Image credit: Nir Friedman
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