When some animals get cold, they regulate their temperature through some pretty straightforward methods. Cold-blooded creatures like lizards bask in the sun to absorb heat and raise their body temperature. Warm-blooded creatures like mammals dilate or constrict their blood vessels. Some animals shiver or pant. But the octopus can't do any of those things. So instead, it hijacks its own genetic information.
According to a new study, when octopuses get chilly, they start a massive RNA editing process.
"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 of the Marine Biological Laboratory of Woods Hole, Massachusetts.
Genetic information from DNA can typically only adapt over the course of generations. Meanwhile, RNA editing offers a temporary way to adapt to environmental changes. RNA editing is a bit like putting on new genetic clothes -- it's not as easy as trying out a new sweater, but you can do it to adapt to a temporary change.
For humans, RNA editing is a very challenging process. We do it, too -- but in a limited fashion. We have millions of sites where RNA is edited in our bodies, but this usually only affects around 3% of our genes. Meanwhile, some octopuses (and other cephalopods) can recode the majority of their proteins.
In 2015, Rosenthal and colleagues were stunned to show just how extensive of an RNA editing ability these animals have. "A big question for us was, 'What are they using it for?'" Rosenthal says.
"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 functions, so the natural question is, are they using this to acclimate to changes in their physical environment?"
Feeling chilly. Let me put on my RNA
To get closer to the answer, they focused on California two-spot octopuses (Octopus bimaculoides) -- a species of octopus native to the coastal waters of California. This species has become a popular species for study in neuroscience and behavior due to its complex nervous system and unusual genetics.
For this particular study, researchers only focused on the effects of temperature. They knew that RNA changes are usually temporary, so they wanted to see whether RNA activity intensifies when octopuses are exposed to the cold. It did.
The researchers split wild-caught adult octopuses into two groups: one group was placed in warm (22ºC) water tanks, while the other was placed in cold (13ºC) waters in tanks at the Marine Biological Laboratory. After several weeks, they compared the RNA transcripts for the two groups, looking at 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.
The team also zoomed in on the proteins that were most encoded by the RNA changes. This was consistent with the findings: the most changes came from proteins associated with cell membranes (which are themselves temperature-sensitive).
The tip of the iceberg
Then, researchers wanted to see how quickly this editing happened. They worked with small octopuses and gradually heated or cooled tanks from 14°C to 24°C, changing the temperature by 0.5°C at every half hour. The entire process took less than a day. During this time, they measured RNA editing before the temperature change, immediately after the temperature change, and up to 4 days afterward. Remarkably, this RNA editing happened within a day of the change.
"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."
Rosenthal suspects that they've only reached the tip of the iceberg, and there could be much more octopus genetic activity we're not aware of yet. This could be linked to their surprisingly developed intelligence and behavior.
Octopuses (and cephalopods) are often considered an "alien" type of intelligence, showing remarkably sophisticated abilities while lacking some of the traits commonly associated with typical intelligence.
"What mechanisms do they use to create this complexity? I believe that RNA editing is one of them," Rosenthal concludes.
Journal Reference: Matthew A. Birk, Noa Liscovitch-Brauer, Matthew J. Dominguez, Sean McNeme, Yang Yue, J. Damon Hoff, Itamar Twersky, Kristen J. Verhey, R. Bryan Sutton, Eli Eisenberg, Joshua J.C. Rosenthal. Temperature-dependent RNA editing in octopus extensively recodes the neural proteome. Cell, 2023; 186 (12): 2544 DOI: 10.1016/j.cell.2023.05.004