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Octopuses rewire their brains to adapt to seasonal temperature shifts

Peer-Reviewed Publication

Cell Press

California two spot octopuses (Octopus bimaculoides) rewire their brains to adapt to seasonal temperature shifts

image: This is a photo of a California two spot octopus (Octopus bimaculoides). view more 

Credit: Tom Kleindinst

Octopuses don’t thermoregulate, so their powerful brains are exposed to—and potentially threatened by—changes in temperature. Researchers report June 8 in the journal Cell that two-spot octopuses adapt to seasonal temperature shifts by producing different neural proteins under warm versus cool conditions. The octopuses achieve this by editing their RNA, the messenger molecule between DNA and proteins. This rewiring likely protects their brains, and the researchers suspect that this unusual strategy is used widely amongst octopuses and squid.

“We generally think that our genetic information is fixed, but the environment can influence how you encode proteins, and in cephalopods this happens on a massive scale,” says senior author Joshua Rosenthal (@joshrosenthal16) of the Marine Biological Laboratory of Woods Hole, Massachusetts.

Compared to DNA mutations, which allow organisms to adapt over the course of generations, RNA editing offers a temporary and flexible way for individuals to adapt to environmental changes. RNA editing occurs across the tree of life, but RNA recoding—when the editing changes the subsequent protein structure—is much rarer, except in soft-bodied cephalopods like octopuses and squid. Humans have millions of editing sites but editing affects the protein products in only ~3% of their genes, whereas coleoid or “smart” cephalopods recode the majority of their neural proteins.

“RNA recoding gives organisms the option to express a diverse quiver of proteins when and where they choose,” says Rosenthal. “In cephalopods, most of the recoding is for proteins that are really important for nervous system function, so the natural question is, are they using this to acclimate to changes in their physical environment?”

To address this question, the research team explored whether octopuses undergo RNA editing in response to shifts in temperature and whether this editing impacts the function of their brain proteins. In the wild, octopuses are exposed to changes in temperature that can occur both rapidly, for example, when they dive to colder depths or there is upwelling, and slowly, when the seasons change.

The team focused on California two-spot octopuses (Octopus bimaculoides)—small, yellowish-brown octopuses who sport two iridescent blue false eyes under their real eyes. These octopuses live off the coast of California and Mexico, and their genome has already been sequenced.

To investigate whether RNA editing is associated with temperature variation, the researchers acclimated wild-caught adult octopuses to warm (22ºC) or cold (13ºC) waters in tanks at the Marine Biological Laboratory. After several weeks, they compared the RNA transcripts for the cold- and warm-acclimated octopuses to the genome to look for signs of RNA editing at over 60,000 previously identified editing sites.

“Temperature-sensitive editing occurred at about one third of our sites—over 20,000 individual places—so this is not something that happens here or there; this is a global phenomenon” says co-senior author Eli Eisenberg of Tel-Aviv University, who handled the computational aspects of the study. “But that being said, it does not happen equally: proteins that are edited tend to be neural proteins, and almost all sites that are temperature sensitive are more highly edited in the cold.”

They also noticed that certain types of neural proteins were more likely to be sensitive to temperature, for example, proteins that are associated with cell membranes (which are themselves very temperature-sensitive) and calcium-binding proteins.

Next, the team explored how quickly these changes occurred. Working with thumbnail-sized juvenile octopuses this time, the researchers gradually heated or cooled tanks—from 14°C to 24°C or vice versa at 0.5°C hourly increments—over the course of about 20 hours and measured the extent of RNA editing at several time points: before the temperature change, immediately after the temperature change was complete, and up to 4 days later. They were surprised by how rapidly RNA editing occurred.

“We had no real idea how quickly this can occur: whether it takes weeks or hours” says first author Matthew Birk, who led the project as a postdoctoral fellow at the Marine Biological Laboratory and is now an assistant professor at Saint Francis University. “We could see significant changes in less than a day, and within 4 days, they were at the new steady-state levels that you find them in after a month.”

Next, in collaboration with Kristen Verhey at University of Michigan and Roger Sutton at Texas Tech, the team explored whether this recoding impacted protein structure function. They focused on kinesin and synaptotagmin, two proteins that are critical for nervous system function, and compared the edited and unedited versions of each protein. In both cases, they found evidence that the recoding produced structural changes in the proteins that would impact their function.

They also showed that temperature-sensitive RNA editing occurs in wild octopuses in response to seasonal temperature fluctuations. Wild octopuses captured in winter versus summer displayed similar patterns of temperature-sensitive RNA editing to those observed in the lab. This was true not only for California two spot octopuses but also for the closely related Verrill’s two-spot octopus (Octopus bimaculatus), and the researchers suspect that temperature-sensitive RNA editing occurs widely among other octopuses and squid.

Open questions remain about how the octopuses are regulating this RNA editing, and it’s unclear why editing occurs more frequently in response to cold temperatures.

Next, the researchers want to explore whether octopuses and other cephalopods use RNA recoding to adapt to other environmental variables, such as low oxygen availability or varied social environments.


This research was supported by the National Science Foundation, the National Institutes of Health, and the United States-Israel Binational Science Foundation.

Cell, Birk et al. “Temperature-dependent RNA editing in octopus extensively recodes the neural proteome” DOI: 10.1016/j.cell.2023.05.004

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