Ability To Rewrite Their Own RNA May Be Behind Octopus Intelligence

Octopuses are alien life among us. They are able to use tools, have three hearts, their arms contain 2/3 of the neurons in an octopuses body and almost have minds of their own, their blood is based on copper rather than iron, and is blue, and are thought to be the most intelligent invertebrates and an important example of advanced cognitive evolution in animals.

They also have a special way of using their genes.

Octopuses, along with other cephalopods such as squid and cuttlefish, often do not follow the genetic instructions in their DNA exactly. They use enzymes to pick out specific adenosine RNA bases (some of As, out of the As, Ts, Gs, and Us of RNA) that code for proteins and replace them with a different base, called Inosine.

This process — called “RNA editing” — is rarely used to recode proteins in most animals, but octopuses and their relatives edit RNA base pairs in over half of their transcribed genes.

When researchers did experiments to quantify and characterize the extent of this RNA editing across cephalopod species, they found evidence that this genetic strategy has profoundly constrained evolution of the cephalopod genome.

Previous research has found that octopuses use RNA editing to rapidly adapt to temperature changes and that the majority of RNA transcripts in squid neurons contain these edits. In this new study, researchers wanted to find out how commonplace these edits are, how they evolved along the cephalopod lineage, and how such extraordinary editing capabilities affect the evolution of the cephalopod genome.

RNA Editing The Rule

Vertebrate cells are capable of RNA editing. But evidence of amino acid re-coding has only been found to a very limited extent in the few species investigated so far.

Humans have 20,000 genes but only a few dozen conserved RNA editing sites that are likely encoding functional proteins.

Squids also have about 20,000 genes but have at least 11,000 active RNA editing sites affecting the proteome, many of which are conserved, according to this study’s estimates. Co-author Eli Eisenberg, a biophysicist at Tel Aviv University, said:

“Basically, this is a mechanism to make proteins that are not encoded in the DNA. They are not present in the genomic sequence. With these cephalopods, this is not the exception. This is the rule. The rule is that most of the proteins are being edited.”

In fact, RNA editing is so rare that it’s not considered part of genetics’ “Central Dogma.” Co-author Joshua Rosenthal, a cephalopod neurobiologist at the Marine Biological Laboratory in Woods Hole, explains:

“Ever since Watson and Crick figured out that genetic information is stored in DNA, we’ve had this view that all the information is stored in DNA, and it’s faithfully copied to another molecule when it’s used—that’s RNA, and from there, it’s translated into the proteins that do all the work. “And it’s generally assumed that that’s a pretty faithful process. What the squid RNA is showing is that that’s not always the case—that, in fact, organisms have developed a potent means to manipulate information in RNA.”

Slower Evolution

Most organisms extensively use splicing, the process of cutting or adding whole sections of RNA transcripts before they leave the nucleus, to diversify their proteomes, but prioritize DNA flexibility over RNA editing.

“We usually think of evolution using whatever it can to answer some challenges—so why was RNA recoding not used?” says Eisenberg. “Now, we have an example of what happens when we do use RNA editing abundantly. We know there’s a price. The price is slowing down genome evolution…Cephalopods probably chose to take this RNA bargain over genome evolution, and maybe vertebrates made the other choice—they preferred genome evolution over editing.”

Since many of the most heavily edited RNAs coded for key neural proteins, the researchers wonder whether RNA editing might contribute to the remarkable intelligence of octopuses and their kin.

Octopus bimaculoides

Octopus bimaculoides (California two-spot octopus) showing its namesake blue spot. This is the only cepalopod species that has been sequenced (in 2015). Credit: Tom Kleindinst

Not only are they smart enough to hunt, octopuses are clever enough to escape from jars, use coconut husks to hide themselves, signal to others by changing their skin color, and learn through observation.

“They’re the only taxon out there that approaches vertebrates in terms of behavioral complexity,” says Rosenthal. “These behaviorally complex coeloids all have this tremendous RNA editing, particularly in their nervous system, where they’re recoding the messenger RNAs that encode for the very things that are important for electrical excitability.”

Researchers are working on an octopus animal model to find out whether RNA editing plays a pivotal role in cephalopod behavior. Experiments that deal with the role of RNA editing in behavior will require an octopus that grows well in laboratories and can be genetically manipulated.

Study: Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods

Top Image: Matthias Kabel, CC BY 2.5