Researchers in Berlin and New York may have solved a long-standing evolutionary mystery: how cephalopods such as octopuses, squids and cuttlefish developed far more complex nervous systems and sophisticated cognitive abilities compared to other invertebrates. They report these capabilities may be linked to a dramatic expansion in microRNA (miRNA) diversity, similar to what occurred in the evolutionary path of the more advanced vertebrates.
From an evolutionary perspective, octopuses are unique among invertebrates. They have both a central brain and a peripheral nervous system capable of acting independently. If an octopus loses a tentacle, the tentacle remains sensitive to touch and can still move. The reason why octopuses are alone in having developed such complex brain functions could lie in the fact that they use their arms very purposefully—as tools to open shells, for example. Octopuses also show other signs of intelligence, exhibiting curiosity and ability to remember things. They can recognize people and show preference for some individuals over others. They are even thought to experience dreams since they change their color and skin structures while sleeping.
A new study from a team at Max Delbrück Center for Molecular Medicine in The Helmholtz Association and Dartmouth College suggest miRNAs, which encode small pieces of RNA that bind to messenger RNA and thus influence protein production, may be the source of this leading intelligence among invertebrates. These binding sites were also conserved throughout cephalopod evolution—another indication that they are of functional importance.
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Professor Nikolaus Rajewsky, Scientific Director of the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB), head of the Systems Biology of Gene Regulatory Elements Lab, says his fascination with octopuses began years ago, during an evening visit to the Monterey Bay Aquarium in California. “I saw this creature sitting on the bottom of the tank and we spent several minutes—so I thought—looking at each other.” He says that looking at an octopus is very different to looking at a fish. “It’s not very scientific, but their eyes do exude a sense of intelligence,” he adds.
In 2019, Rajewsky read a publication about genetic analyses conducted on octopuses. Scientists had discovered that a lot of RNA editing occurs in these cephalopods, meaning they make extensive use of certain enzymes that can recode their RNA. “This got me thinking that octopuses may not only be good at editing, but could have other RNA tricks up their sleeve too,” says Rajewsky. So, he began a collaboration with the Stazione Zoologica Anton Dohrn marine research station in Naples, which sent him samples of 18 different tissue types from dead octopuses.
Tissue analysis of the samples found that octopuses possess a massively expanded repertoire of miRNAs in their neural tissue, similar to developments that occurred in vertebrates. These results were surprising. “There was indeed a lot of RNA editing going on, but not in areas that we believe to be of interest,” says Rajewsky. The most interesting discovery was the dramatic expansion of microRNAs. A total of 42 novel miRNA families were found in neural tissue, and mostly in the brain. Given that these genes were conserved during cephalopod evolution, the team concludes they were clearly beneficial to the animals and are therefore functionally important.
“This is the third-largest expansion of microRNA families in the animal world, and the largest outside of vertebrates,” says lead author Grygoriy Zolotarov, MD, a Ukrainian scientist who interned in Rajewsky’s lab at MDC-BIMSB. “To give you an idea of the scale, oysters, which are also mollusks, have acquired just five new microRNA families since the last ancestors they shared with octopuses—while the octopuses have acquired 90!” Oysters, adds Zolotarov, aren’t exactly known for their intelligence.
Rajewsky says the findings, reported in the journal Science Advances, point to miRNAs playing a fundamental role in the development of complex brains. He is now planning to partner with other octopus researchers to form a European network that will allow greater exchange between the scientists. Although the community is currently small, Rajewsky says that interest in octopuses is growing worldwide, including among behavioral researchers.
Meanwhile, Rajewsky and his team are now planning to apply a technique, developed in Rajewsky’s lab, which will make the cells in octopus tissue visible at a molecular level. “Since octopuses aren’t typical model organisms, our molecular-biological tools were very limited,” says Zolotarov. “So we don’t yet know exactly which types of cell express the new microRNAs.”