Biology for Worldbuilding: Immutably Mutable Genetics of Octopuses

[Above: Drawing of Octopus vulgaris by Comingio Merculiano (1845-1915) circa 1896, published in Jatta Giuseppe (1860-1903). Public Domain via Wikimedia Commons.]

This post is the first in the series aimed at people who write speculative fiction–sci-fi, fantasy, horror, etc–and are looking for worldbuilding inspiration. In each post, we’ll take a look at a biological trait and explore how that trait might shape a species and the cultures/societies said species might form. Since these posts are mostly about hypothetical alien or fantasy worlds, I want to stress that these posts are thought experiments and highly spectulative.

Humans cultures are obsessed with the idea of inheriting fixed traits–such as nobility, honesty, and magical abilities–from ancestors. It’s the basis of feudalism and hereditary rule. It’s at the root of the Nature vs. Nurture debate. And today, it’s one of the main reasons why people get their genomes sequenced. The concepts of DNA and bloodlines will probably be used to justify racism, power grabs, and high fantasy plot twists for decades to come.

Thanks to DNA sequencing studies, the evidence is pretty clear: many traits and predispositions to certain traits can be passed down from parent to parent. People still tend to assume that traits–especially physical ones and “innate” abilities–are more or less determined by DNA and that the environment’s role, if it has one, is secondary. After all, you can’t just rewrite your own genetic code, right?

Well…if you’re an octopus, squid, or cuttlefish, you kind of can…at the RNA level, anyway.

That, imho, would be an interesting trait for a sci-fi alien or fantasy beastie to have, and in sentient, society-forming life forms, it could have a profound impact on how they behave and see themselves.

[Flamboyant cuttlefish doesn’t care who Jon Snow’s parents are.] via GIPHY

First, some science explanation:

Octopuses, squid, and cutteflish–collectively known as the “coleoid cephalopods“–transcribe the sequences in their DNA into RNA pretty much the way everyone else does, but then, they add an extra step that allows them to make proteins that aren’t encoded in their genomes: They have enzymes that pull As, Gs, Cs, and Ts off of the RNA backbone and replace them with new base pairs in a process called RNA editing.

Mammals and other animals can edit our RNAs and do have the RNA-editing enzymes floating around in our cells, but we don’t use the ability very often. RNA-editor enzymes are very picky and can only edit base pairs that are flanked by specific sequences. (If you want to get especially specific about it, an RNA-editing target has to be surrounded by base pairs that allow the RNA to tie itself up in a knot with the target sticking out.) For our purposes, the thing you need to remember is that: octopuses and company can alter the proteins their cells are making very rapidly by rewriting their RNA, and they do it all the time.

That ability can be useful for quickly adjusting to cold water or in neurons that need to be able to respond to cues quickly in general. But it comes with a catch.

This is how I described the catch in one of my favorite press releases that I wrote during my internship at Cell Press.

“If the bases on either side of the editing target mutate, then the organism may lose the ability to edit that target. Avid RNA recoders, like octopuses and squid, cannot afford DNA mutations in their RNA-editable genes, so they’ve surrendered the benefits of a frequently mutating DNA genome in favor of RNA editing, the researchers found.”

In other words: Octopuses, squids, and cuttlefish can go off-blueprint, but they have to keep their DNA genome unchanged to preserve that ability.

RNA editing is faster than most other forms of molecular gene hacking, so it’s great for responding to sudden shifts in your environment, but DNA mutation is also super-useful, because it gives your offspring a chance to adapt.

In cephalopod evolution, nature favored rapidfire RNA mods at the expense of a static genome. In other animals’ evolution, it favored the opposite: DNA mutations that can be passed down through generations but with relatively little RNA tampering.

This trade-off becomes even more intriguing when you realize that octopuses, squids, and cuttlefish are the most intelligent non-mammals on the planet. Many of their key neural genes have lots of RNA editing sites, and their less-intelligent relatives–the chambered nautiloids–don’t edit their RNAs with the same abandon. The evidence is circumstantial, but researchers are definitely curious about whether RNA editing contributes to the coeloid cephalopods’ intelligence.

The octopuses, squids, and cuttlefish on our planet are excellent hunters, tricksters, and communicators, but as far as we know, don’t have a society/culture. (If you want to learn more about our planets “aliens”-in-residence, Massive is keeping a running list of standout cephalopod stories.)

However, if a group of RNA editing organisms did form their own society, I think they might develop very different ideas about government, responsibility, and identity.

Why change yourself when you can change the world?

[Jar-Opening Octopus Waits for No One to Rescue Them] via GIPHY

I want one thing to be crystal clear here: Octopuses cannot just think to themselves, “I’m going to modify my RNA today.”

The RNA edits happen at a cellular level; they are involuntary.

(Unless the octopus is in a Bene Gesserit-like organization where they learn exert extreme control over their bodies through mindfulness . I’ll circle back to this later.)

For your average Tentacles McGee, daily life with prolific RNA editing would look something like this:

You wake up in your a warm, toasty home, scarf down a whelk for breakfast, and jet off to work. But suddenly, you realize that you’ve swum into a patch of cold water. You feel your hearts speeding up and your senses shifting, because the electrical synapse patterns throughout your body are changing. Within a few minutes, your attitude, your walk, and your reflexes have changed.

The above scenario is loosely inspired by a 2012 Science paper that found octopus cells build a different style of electron-transmitting protein gates in cold water than they do in warm water. They didn’t look into RNA-edit-driven behavior, but if your character is like those octopuses, a wintry outside environment could set off profound physiological changes in every cell in their body.

It’s not hard to imagine that changing up ion channels in all your character’s neurons could alter their perception, personality, ability to retain memories, or even physical abilities. Maybe subtly, maybe a lot.

[From here on out, this post will mostly be me making stuff up. Hopefully in a logical/semi-plausible way, but still…]

In a hypothetical society full of RNA-editing frequent fliers, arguments about who controls the office thermostat could actually be make-or-break struggles because a person who’s a genius at 35 degrees Celsius could be totally incompetent at 31 degrees.

Temperature isn’t the only potential cue for setting of RNA editing cascades. Dehydration, the presence or absence of certain chemicals (or other characters), and a myriad of other factors could theoretically induce RNA editing. Instead of allergies, RNA-editing characters could have alternate personalities during pollen season (or coral spawning season if they live underwater).

And who knows? Maybe the Hulk hulks-out because when his adrenaline levels hit a certain level, it triggers RNA editing.

via GIPHY

In some ways, RNA-editing induced changes are not so different from our own responses to the world. Our behavior changes when we’re cold, dehydrated, or full of adrenaline. But with RNA-editing characters, you could justify more dramatic mental and physical changes.

RNA editors seeking to become their best selves would probably put A LOT of effort into controlling the environment around them. Mindfulness, meditation, positivity, and the like might help them control internal chemical triggers like adrenaline, but to manage body changes caused by external temperature or allergens, they’d have to control the climate around them. It could also be really easy to sabotage an RNA editor, so I‘d anticipate that a society full of them would be characterized by conflicts and power struggles over who contols the surrounding environment.

(Mind you, these hypothetical RNA editors wouldn’t need to be at a technological/science level where they know why they’re so susceptible to environmental shifts. If you belong to a race of people whose personalities change with the weather, you’d notice it, even in antiquity, and there would probably be some very interesting folklore about why these changes happen.)

I’d hypothesize that a society of RNA editors would see themselves as very much connected to the environment. They wouldn’t be able to divide the world into “civilization” (us) and “wilderness” (them), the way modern Western societies do. Ecological catastrophes would be recognized as catastrophic, and you could probably write a pretty interesting story about such a society facing crisis because they’ve mangled their environment such that they can no longer produce the geniuses they need to fix it.

Identity & Inheritance

“This is the excellent foppery of the world, that, when we are sick in fortune, often the surfeit of our own behaviour, we make guilty of our disasters the sun, the moon, and the stars; as if we were villains on necessity; fools by heavenly compulsion; knaves, thieves, and treachers by spherical pre-dominance; drunkards, liars, and adulterers by an enforc’d obedience of planetary influence; and all that we are evil in, by a divine thrusting on.” -Edmund (a bastard), Shakespeare’s King Lear, Act I: Scene 2

Humans–especially modern ones–spend a lot of time trying to find themselves, define themselves, figure out whether they are their parents’ child, and show who they are inside, but all of those pursuits assume that there’s a fixed self.

Beings who are super-susceptible to environmental changes and whose personalities change on a daily basis might not think in terms of having fixed selves at all.

That’s hard to wrap your head around, because it changes almost everything. Many ancient storylines revolve around mistaken identities and trying to divine who a child’s parents are by scrutinizing their features, but if their features and behavior are more driven by the environment around them, searching for markers of fixed identity and heritage would be infinitely more difficult.

I think that in a society of RNA editors contemplating identity, two things would likely happen:

(a) Identity would be less about “who you are” and “who your parents are” but instead about “where you are” and “what you’ve done”.

(b) The characters would come up with an elaborate system of blaming their circumstances on external conditions and Divine Intervention (as Edmund describes above but more extensive.)

It might be harder to swing an argument about “Divine Right” to rule in an RNA editor society. (Alternatively, if the sentient RNA editors are one of just a few species that can shapeshift and be changed by their environment, they could use that as an argument that they are divinely chosen and more deeply connected to the world than other forms of life.)

These issues might get even more complicated for our RNA-editing characters if they live in a society that understands molecular biology and its own genetics.

Remember what I said earlier: RNA editors have to keep their genome mostly unchanged; otherwise they lose their RNA editing sites. The genetic foundation must be kept immutable in order to accomodate changeability.

In other words, a society of people that have always thought of themselves as products of their environments and circumstance might suddenly be confronted by the idea that they carry an ancient and largely unchanged “blueprint” or essence of their species in their DNA. That might melt their brains a little bit.

Or they might take it in stride. In that case, DNA mutations might be viewed not as abberrations that enable adaptation but as restrictions that prevent adaptation.

I think that, in any case, RNA editor society would probably have a non-linear vision of progress/advancement/evolution, because so many of their physiological traits can be changed or reversed.

Which honestly sets them up to be better biologists than most humans. These characters might be able to feel ecological changes impacting their bodies, recognize than there is no “more evolved” but only “better adapted to present circumstances, and know that a genome isn’t a fixed text; it’s a toolkit that encodes for possibilities. As someone steeped in 21st century biology, that’s how I think about the world: complex, interdependent, and malleable.

Octopus as Bene Gesserit; Bene Gesserit as Octopus?

[Turning dark and standing tall is Octopus for “Back the F**K Off!” at least in some species.] via GIPHY

If you’ve been reading this post thinking, “But, dammit, I want to have a hard science justification for a character who can change their own biology at will,” I have good news and bad news.

The good news: Our real-world RNA editors–octopuses, squids, and cuttlefishes–are arguably the real world’s most competent shapeshifters. They have a nervous system that allows them to change their colors and textures in an instant, and more importantly, they don’t have to go into a coccoon, liquefy themselves, and start from scratch like a caterpillar. We don’t know whether RNA editing contributes to their shape-shifting ability, but I personally wouldn’t be surprised if it did.

The other bit of good news: Other animals, including humans, have RNA editing proteins, too. We just don’t use ours very much. The human genome has roughly the same number of genes as squid, octopus, and cuttlefish genomes do, but we only have a few dozen places in our coding genome where RNA-editing-proteins can bind. Squids, on the other hand, have at least ~11,000, according to the most recent study. (And yes, squids, and by extension, krakens are in RNA-editor club.)



The researchers don’t know why natural selection sent the coleoid cephalods down the evolutionary road less traveled, but they told me that they suspect that octopuses’ versions of RNA-editor protein have mutated (millions of years ago) such that they function more effectively than ours. (This is just a suspicion; they don’t have any details of what exactly is different in coleoids pinned down yet.)

But if we play the wild-Sci-Fi-speculation game, it may theoretically be possible to splice the gene for the Octopus-versions of RNA editor proteins into other organisms. With gene engineering, we could also theoretically add more RNA editing sites into our own genome.

That would probably be a bad idea, but you could make a case that your human with exceptional control over their physiology is a genetic experiment or descended from genetic experiments in enhanced RNA editing.

The bad news is: I still don’t see how a person would be able to turn their RNA editing on and off at will. You can turn your genes on and off; in fact, transcription factors are doing that right now in cells throughout your body, but can you feel it? Can you control it?

You can set off a whole bunch of molecular changes in your body by going jogging or something, but you can’t control the individual genes and molecules. So I think for RNA editors, regulating their genetic improvisation would work similarly, through healthy practices and behaviors that can trigger changes broadly but not precisely.

Octopuses and cuttlefishes are really good at changing their skin colors to blend in with stuff, but I don’t think coleoid-style RNA editing would allow a human person to alter their bone structure into an exact replica of someone else’s face. Face-swapping would still be magic.

And even in the case of milder molecular control, it still seems like a longshot. [Mild Dune spoiler ahead] In Frank Herbert’s Dune, there are these women called the Bene Gesserit who can do many borderline magical things, including determining the sex of a child while in the act of conceiving. While it’s fun to imagine that original Bene Gesserits were products of genetic engineering with cuttlefish RNA-editing enzymes spliced into their genes to give them super-human control over their own cellular & neural function, I still have no idea how they would perceive what’s happening inside their bodies at the molecular level.

So, in conclusion, I would say that RNA-editing is a prime candidate for use in sci-fi and fantasy worldbuilding and a slightly more plausible explanation for shapeshifting than most, but yeah…Consciously-controlled shapeshifting is still pretty fantastical.

[That’s all for now!] via GIPHY

TL;DR:

Octopuses, squids, and cuttlefish can make proteins that aren’t in their DNA genome by editing their RNA. And that’s a trait that world-building sci-fi and fantasy writers could have a field day with.

Papers Referenced:

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