Cephalopods like squids may be as close to an alien intelligence as we’ll ever know, with a diverse evolutionary lineage from a wholly different world beneath the waves.
Yet despite our uniquely developed brains and bodies, we are all works in progress through a common process.
Humans and other animals constantly undergo an ephemeral, reversible transcriptomic remixing through what’s known as ‘adenosine deaminase acting on RNA’ or ADAR-mediated RNA editing.
In simplified terms, this is like printing a recipe but changing raisins to chocolate chips right before handing it to the baker.
No other creatures may do this as well as coleoid cephalopods – which include the smart and squishy squid, octopus, and cuttlefish – and it’s not even close.
These cephalopods’ RNA seems to be more malleable than the Skyrim character creator, leading to altered proteins that sometimes boost biological abilities on an extraordinary scale, new research demonstrates.
In a study published in the journal Cell, a research team led by bioscientists from the University of California, San Francisco (UCSF), explored the proteome – the complete complement of approximately 24,000 proteins – of the longfin inshore squid (Doryteuthis pealeii), to ascertain what these edits actually do.
The biggest surprise may have been the breadth of the edits’ effects.
“We found effects on protein activity, stability, localization, and even how they interact with other proteins. The downstream effects even go so far as to regulate organelle health,” first author Jack Moen, a cellular and molecular scientist at UCSF, told ScienceAlert.
“By editing the RNA instructions used to make proteins, these animals can generate proteins with different properties, all without changing their DNA.”
Before this work, relatively little was known about these changes. But they have previously been shown to influence central nervous system communication, perhaps in response to environmental or physiological conditions, such as temperature fluctuations, the researchers say in the paper.
To discover extra effects, they explored nearly 8,000 sites where proteins were edited across more than 2,000 different proteins in the squid optic lobe and the gills. This allowed a comparison of RNA-editing activity in the sophisticated squid brain versus the more ‘janitorial’ respiratory organ.
The optic lobe, responsible for seeing things and responding to them, comprises a sizable part of a squid’s central nervous system, and it displays frequent, more complex editing activity.
This may make sense, as cephalopods possess the most robust ADAR-editing ability and the most complex nervous systems seen in invertebrates – features that emerged together, the researchers suggest.
Importantly, such edits occur in protein-coding sequences rather than in the non-protein-coding ‘junk’ parts of their genome.
Some of these changes occur in the ADAR proteins, as the molecular workers themselves become altered to offer a level of gene-balancing or self-regulation.
“Another result that struck us was the potential to create new protein sequences,” Moen adds, as they identified 5,000 short proteins that were not in the reference squid proteome or in the gold-standard Swiss-Prot database of 14,000 organisms.
A good (or random) baker will always make different types of cookies.
The editing action also changes where the proteins are found; their altered forms hit the road, moving from the cells’ outskirts toward the nucleus, or cellular headquarters.
This protein recoding can change the action of organelles (the cells’ version of organs) like mitochondria, and even those who dozed during physio know these are the essential, energy-making ‘powerhouses of the cell’.
Actually, the researchers found that this recoding may make squid mitochondria more similar to human mitochondria: more environmentally stable and better able to recycle themselves.
Similarly, recoding also seems to affect their creatine systems to provide bursts of squidly energy for evasive movements or other complex brain processes.
Amazingly, this all occurs by editing a base at a time. In fact, that’s the point, because it doesn’t change the DNA master blueprint and potentially pass down harmful mutations – a proteomic free trial, no credit card info required.
All up, the findings show that cephalopods are even more alien-ish than we’ve been giving them credit for, maintaining an unmatched level of genetic flexibility.
But why does this apply to cephalopods and not other animals?
It’s due to the structures of the ADAR enzymes, but also for other reasons that require more research, Moen explains.
The theoretical possibilities are overwhelming and beyond astronomical, with more protein variants than all the stars, planets, and super-alcohol clouds in the Universe combined.
“If we look at all of the sites identified in the RNA sequencing data, it brings the theoretical estimate closer to 10²⁴⁸,” Moen told ScienceAlert.
That is well over 100 orders of magnitude greater than all the atoms in the Universe.
It therefore represents a fundamental duality between natural potential and actuality.
“They describe an enormous potential diversity,” Moen said. How much of it the animals actually produce remains unknown.”
The research has been published in Cell.
This article was fact-checked by Rachel Garner and edited by Peter Dockrill. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
