Octopuses are some of the smartest animals on Earth – and some of the strangest. They have about the same number of neurons as dogs, but more than half of those cells are distributed among the smooth cephalopods’ eight arms rather than in a central brain.
As researchers report on June 8 in Cell, the neural anomalies only get more bizarre from there. Octopuses, they discovered, have the ability to recode their neurons in response to temperature shifts, so those cells produce different proteins. Like humans who change their clothes to match the weather outside, octopuses edit their RNA, a genetic molecule that carries DNA’s instructions to produce proteins — the workhorses of cells. The researchers suspect those “brain edits” help octopuses adapt to heat or cold as the seasons change. And they do this to an “extraordinary degree,” says co-senior author Joshua Rosenthal, a biologist at the Marine Biological Laboratory in Woods Hole, Massachusetts.
RNA editing occurs when an outside force activates certain enzymes in the body’s cells which then make chemical changes to the RNA. Depending on the changes, the cells produce different forms or isoforms of proteins. Because RNA is a transient molecule, any changes to the genetic information it contains won’t be permanent — a property that theoretically makes it a powerful tool for acclimatizing to changing environmental conditions along the way.
In humans, RNA editing affects protein production in less than 3 percent of genes, while Rosenthal and colleagues previously found that all sophisticated species of cephalopods— that is, all cephalopods except nautiluses — can recode most neural proteins.
The researchers wanted to follow up on that previous work to see what factors might stimulate RNA editing in cephalopods. They started with temperature change because it is a simple environmental condition that fluctuates seasonally or even daily.
The scientists first collected a dozen wild California two-spot octopuses (Octopus bimaculoides), a species whose genome has already been sequenced. They accustomed the animals to tanks of warm or cold water. A few weeks later, the researchers examined about 60,000 previously identified places in the genomes of the animals where enzymes edit RNA. They found that about a third of those sites had changed and that these changes happened quickly, on a scale of hours to several days. “We expected to see a few sites here and there that had changed, but no, this was something very global,” said co-senior author Eli Eisenberg, a physicist at Tel Aviv University whose research focuses on RNA.
Nearly all of the changes were caused by cold, the team found. And among those changes were those that coded for specific classes of proteins involved in cell membranes, functions of synapses (which transmit neuronal signals), autophagy (programmed cell death), and the binding of calcium (which plays different roles within neurons). The researchers confirmed that the isoforms made through the edited RNA had altered functions, but “we don’t yet know how these thousands of changes, or some of them, promote adaptation,” says Eisenberg. “Understanding the global effect of all concerted changes is left to future research.”
Finally, the team also collected wild octopuses, including another closely related species, Verrill’s two-spot octopus (Octopus bimaculatus)—summer and winter. Those individuals, the researchers found, showed the same temperature-tracking RNA-related changes as the California two-spot octopuses they tested in the lab.
Unlike humans and other mammals, octopuses cannot regulate their own temperature. So the researchers suspect that RNA editing plays a role in protecting invertebrate neurons from temperature fluctuations. “The organism chooses to express different isoforms, and each is better in its own state,” says Eisenberg. “There’s not even a single example of that happening in mammals.”
Heather Hundley, a biologist at Indiana University Bloomington who was not involved in the study, calls the new paper “a real tour de force”.
“This work adds to the growing body of data showing that RNA editing can be dynamically regulated,” she says. “While previous work has focused primarily on regulation during development and disease, this work demonstrates that RNA editing can serve as a molecular means of acclimating protein function in response to environmental changes in temperature.”
Rosenthal, Eisenberg and their colleagues plan to continue this line of research by investigating additional factors that can cause changes in protein production, such as pH and oxygen levels or the social environment. “How broad is this ability to acclimate through RNA editing?” Rosenthal says. “There’s a lot of interesting work to be done.”
