Unique cellular trick could explain octopuses’ intelligence

When it comes to animal intelligence, octopuses have few rivals. Some species of cephalopods carry coconut shells as mobile shelter; others radically transform their bodies to mimic deadlier creatures. Nearly twenty years ago in Germany, a particularly cunning octopus named Otto short-circuited his aquarium’s electrical system by spraying jets of water onto a ceiling light, which may have caused an unpleasant glare.

Octopuses are also intelligentin their own way, like famous animals like crows, dolphins or chimpanzees. But they have a fundamentally different intelligence, shaped by a distinct evolutionary path and defined by a nervous system that is distributed throughout their body rather than centralized like that of the brain of most animals.

Researchers have discovered another surprise in octopus biology: a mutation, never documented in any other animal, that makes their cells remarkably precise in creating proteins and this appeared just as they were beginning to develop large nervous systems. “We cannot establish a direct relationship [between] a slight change in the precision of protein synthesis and in what is called advanced intelligence,” says Nicholas Bellono, a molecular biologist at Harvard University. But he notes that the timing “fits perfectly” with the emergence of sophisticated behaviors in octopuses.

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Bellono and his colleagues, who published their work today in Current biologystumbled upon this evolutionary innovation. Co-lead author Richard Han, then a graduate student in the lab of Amy Lee, a cell biologist at Harvard Medical School, was examining octopus RNA — the molecules that carry the genetic instructions that cells use to build proteins — when he noticed an unusual break in the genetic sequences that formed ribosomes, the cell’s protein-producing machinery. This ribosomal RNA (rRNA) sequence is identical in all other animals studied, so the deviation jumped out at Han. “Finding a difference here was really unexpected for us,” he says.

To understand how this break affected the function of the ribosome, the researchers integrated it Escherichia coli bacteria. The engineered bacteria made fewer mistakes when building proteins, reducing the risk of misfolded molecules clumping together into toxic, disease-causing aggregates. Next, the researchers compared tissues from octopus and squid and found that the former actually contained fewer and smaller clumps of protein.

Although the benefits are obvious, it is unclear why only octopuses developed this rRNA break. This appears exclusive to shallow-water octopus species, which split from their deep-sea counterparts around 100 million years ago to colonize a very complex environment. Faced with more predators, prey, and competition, their nervous systems quickly developed to meet the new demands. And neurons, because of their long lifespan, are particularly vulnerable to protein clumps, according to the new study’s co-senior author, Rishav Mitra, a postdoctoral researcher in Bellono’s lab. By preventing misfolded proteins, he says, breaking rRNA “could help these neurons function well.”

Other researchers say a link between snapping and octopus intelligence is plausible, although it lacks direct evidence. “These associations are intriguing,” says Eli Eisenberg, a geneticist at Tel Aviv University who was not involved in the study, “but further evidence is needed to support the hypothesis that they contributed to the evolution of neuronal complexity or cognitive abilities.” To truly establish this link, he says, it would be necessary to modify rRNA breaking and test for changes in learning, sensory processing or problem solving. “These experiments would of course be very difficult,” adds Eisenberg.

The real value of this discovery may lie in its potential applications in health care. In humans, protein clusters play a role in many neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Lee hopes it will be possible to design drugs targeting ribosomes to mimic the octopus’ useful trick for ultra-precise protein synthesis, thereby reducing the burden of misfolded molecules. If we “use nature as a guide to understand how this happens naturally,” she says, “then we can probably find ways to introduce it into human cells.”