Octopuses Evolved a Unique Ribosome to Boost Protein Synthesis Accuracy

The octopus is a biological oddity. It can use tools, open jars, and its complex nervous system supports as many neurons as a small primate. Harvard biologists now report a distinction in octopus core biology: some octopuses carry an unusual adaptation in the protein-making machinery of their cells that helps ensure accuracy, possibly an evolutionary byproduct of their acute sensory system.

In a study published in Current Biology, the researchers describe a structural aberration in the ribosome—the protein-manufacturing organelles of cells—that appears unique in the animal kingdom. “This shows that the ribosome is actually an important part of the evolution of biological novelty across hundreds of millions of years,” said Nicholas Bellono, a senior author of the study. “This opens a different way for people to think about the biochemical basis of comparative biology.”

The finding began with an accidental observation. About five years ago, co-author Richard Han extracted ribosomal RNA (rRNA) from tissues of the California two-spot octopus (Octopus bimaculoides). Normally, such rRNA sequences remain uniform and serve as quality controls. Instead, Han saw the octopus rRNA split into two distinct fragments.

Researchers repeated the experiment and kept finding the same break in the same spot, in all octopus tissues at all developmental stages. Variation in the basic architecture of the ribosome is rare. “The assumption was that this doesn’t change very much,” said co-author Amy Lee. “That was the real surprise here.”

The team discovered that the shift appears to enhance the accuracy of protein synthesis and reduces errors that cause pathological aggregations of misfolded proteins. When researchers inserted the same rRNA break into the ribosomes of E. coli, the bacteria produced proteins with twice their normal fidelity.

The rRNA break was universal among shallow-water octopuses (the suborder Incirrates), which diverged from deep-water cousins (the Cirrates) about 100 million years ago. A deep-sea cirrate octopus did not possess the same change, nor did squid, which diverged from the octopus lineage about 300 million years ago.

The researchers suspect the adaptation may be tied to the evolution of the large octopus nervous system, including the acutely sensitive “taste by touch” sensory system. Most of the 500 million octopus neurons are in the arms, and a single suction cup contains some 10,000 sensory cells. Cephalopods edit their RNA far more than other organisms, which increases the potential for misfolding and toxic aggregates. Bellono suggested the ribosome feature might serve as a brake or filter. “They have the ability to make many protein products from single genes, but the ribosome will only allow certain ones to be made,” he said.

Lee described the rRNA adaptation as “controlled plasticity for the genetic information.” She added that these discoveries might someday inform therapies for protein-folding diseases such as Alzheimer’s and Parkinson’s. “What’s really cool is that by looking into the natural world, we are potentially starting to identify these hot spots we could target to change function,” she said.