Octopuses are like aliens living among us — they do a lot of things differently from land animals, or even other sea creatures.

Octopuses and squid are masters of RNA editing while leaving DNA intact
These changes could explain the intelligence and flexibility of shell-less cephalopods

Octopuses and other shell-less cephalopods commonly edit their RNA without changing their DNA. Scientists don’t yet know why.

Many writers grouse when an editor makes a change in a story, but the consequences of changing a single word usually aren’t that dire.

Not so with genetic instructions for making proteins. Even a small change can prevent a protein from doing its job properly, with possibly deadly consequences. Only occasionally is a change beneficial. It seems wisest to preserve genetic instructions as they are written. Unless you’re an octopus.

Octopuses are like aliens living among us — they do a lot of things differently from land animals, or even other sea creatures. Their flexible tentacles taste what they touch and have minds of their own. Octopuses’ eyes are color-blind, but their skin can detect light on its own (SN: 6/27/15, p. 10). They are masters of disguise, changing color and skin textures to blend into their surroundings or scare off rivals. And to a greater extent than most creatures, octopuses squirt the molecular equivalent of red ink over their genetic instructions with astounding abandon, like a copy editor run amok.

These edits modify RNA, the molecule used to translate information from the genetic blueprint stored in DNA, while leaving the DNA unaltered.

Scientists don’t yet know for sure why octopuses, and other shell-less cephalopods including squid and cuttlefish, are such prolific editors. Researchers are debating whether this form of genetic editing gave cephalopods an evolutionary leg (or tentacle) up or whether the editing is just a sometimes useful accident. Scientists are also probing what consequences the RNA alterations may have under various conditions. Some evidence suggests editing may give cephalopods some of their smarts but could come at the cost of holding back evolution in their DNA

“These animals are just magical,” says Caroline Albertin, a comparative developmental biologist at the Marine Biological Laboratory in Woods Hole, Mass. “They have all sorts of different solutions to living in the world they come from.” RNA editing may help give the creatures vast numbers of solutions for problems they may face.
Unlike other animals with bilateral symmetry, octopuses don’t crawl in a predetermined direction. Videos of octopuses crawling show they can move in any direction relative to their body, and they change crawling direction independently of turning their bodies. In the clip, the green arrow marks the orientation of the octopus’ body and a blue arrow marks the direction it is crawling.

How cephalopods modify their RNA
Molecular biology’s central dogma holds that instructions for building an organism are contained in DNA. Cells copy those instructions into messenger RNAs, or mRNAs. Then, cellular machinery called ribosomes read the mRNAs to build proteins by stringing amino acids together. Most of the time, the protein’s composition conforms to the DNA template for the protein’s sequence of amino acids.
But RNA editing can cause divergences from the DNA instructions, creating some proteins that have different amino acids than specified by the DNA.

Editing chemically modifies one of RNA’s four building blocks, or bases. Those bases are often referred to by the first letters of their names: A, C, G and U, for adenine, cytosine, guanine and uracil (RNA’s version of the DNA base thymine). In an RNA molecule, the bases are linked to sugars; the adenine-sugar unit, for instance, is referred to as adenosine.
There are many ways to edit RNA letters. Cephalopods excel at a type of editing known as adenosine to inosine, or A-to-I, editing. This happens when an enzyme called ADAR2 strips a nitrogen and two hydrogen atoms off adenosine (the A). That chemical peel turns adenosine into inosine (I).

Ribosomes read inosine as guanine instead of adenine. Sometimes that switch has no effect on the resulting protein’s chain of amino acids. But in some cases, having a G where an A should be results in a different amino acid being inserted into the protein. Such protein-altering RNA editing is called RNA recoding.

Soft-bodied cephalopods have embraced RNA recoding with all of their arms while even closely related species are more tentative about accepting rewrites, Albertin says. “Other mollusks don’t seem to do it” to to the same extent.

RNA editing isn’t limited to creatures of the deep. Almost every multicellular organism has one or more RNA editing enzymes called ADAR enzymes, short for “adenosine deaminase that acts on RNA,” says Joshua Rosenthal, a molecular neurobiologist also at the Marine Biological Laboratory.

Cephalopods have two ADAR enzymes. Humans have versions of them, too. “In our brains, we edit a ton of RNA. We do it a lot,” Rosenthal says. Over the last decade, scientists have discovered millions of places in human RNAs where editing occurs.

But those edits rarely change the amino acids in a protein. For instance, Eli Eisenberg of Tel Aviv University and colleagues identified more than 4.6 million editing sites in human RNAs. Of those, only 1,517 recode proteins, the researchers reported last year in Nature Communications. Of those recoding sites, up to 835 are shared with other mammals, suggesting that evolutionary forces preserved editing at those locations.