As if octopuses, squids and other cephalopods were not already strange enough, they may have found a way to evolve that is foreign to practically all other multicellular organisms on the planet.
For most animals, changes that might prove beneficial to the organism primarily occur at the beginning of their molecular production process. Mutations occur in DNA that are then transcribed into RNA; the RNA is then translated into an altered protein.
Not so for cephalopods—at least not entirely. A new study published in Cell reports these aquarium oddities can modify the proteins found in their bodies without having to change the basic sequence of their DNA blueprint. As a result, it looks as if cephalopods have changed very slowly over the eons of their existence. The findings also suggest that octopuses and their tentacled cousins may be a lot older than previously thought.
The new paper reports on a process called “RNA editing,” which involves enzymes swapping out one RNA base (or nitrogen-based “letter” in the RNA/DNA alphabet) for another, presumably in the interest of an organism adapting to its environment. RNA editing is rarely employed in most animals. Among the 20,000 or so genes found in humans, for example, only a few dozen sites are thought to change their RNA so that it no longer matches the original DNA template.
Yet previous work, in part by the same authors, suggested the process is employed rather frequently by octopuses and squid to respond to changes in ocean water temperature. The new study looked at DNA sequences, RNA sequences and proteomes—meaning all of the proteins encoded in a particularly cell or tissue—of multiple cephalopod species to determine how common RNA editing really is. Very, it turns out.
Squid also have around 20,000 genes, a whopping 11,000 of which code for RNA that in some cases undergoes editing. A similar degree of editing was found in two species of octopus and the common cuttlefish. Far lower levels of RNA-editing were seen in the nautilus—a more primitive cephalopod—and in a non-cephalopod control, a mollusk called a sea hare. RNA editing was especially high in the cephalopod nervous system, including in genes coding for ion channels that facilitate electrical communication between neurons.
What’s more, such extensive RNA editing seems to have helped to minimize changes in the cephalopod DNA over the eons that they have been around. Unlike most animal species, whose genomes are riddled with millions of years of mutations that have helped them adapt to a volatile world, cephalopod adaption appears to have been more a result of RNA editing.
Heavy reliance on RNA editing, however it first evolved, practically would have guaranteed the need for cephalopod DNA to remain fairly stable over millennia. The proteins used for editing RNA would, after all, need to recognize various complexes of RNA, says paper co-author Joshua Rosenthal, a cephalopod neurobiologist at the Marine Biological Laboratory. Hence, the DNA coding for the RNA that generates those particular proteins would have to stay consistent. In other words, in an animal reliant on RNA-editing for survival, any mutations that interfered with that process would probably not have survived into the next generation. “If a squid and octopus want to edit a base, they must preserve the underlying RNA structure,” Rosenthal says, “This means that the RNA structure can’t evolve. If it collects mutations as a result of DNA mutations, it would no longer be recognized by the editing enzymes. We normally think of mutations as the currency of evolution. But in this case their accumulation is suppressed.”
In 2015 University of Chicago neurobiologist Clifton Ragsdale and his team published the first cephalopod genome, that of an octopus. Clifton also noticed an unusually high degree of RNA editing. “We saw the same thing,” he recalls. “But this new paper provides much more information and raises interesting ideas—instead of just using regular old genome evolution, RNA editing might have been a way to produce molecular diversity, particularly in their nervous systems. You could imagine that it’s an alternative engine for cephalopod evolution.”
Why Edit RNA?
No one knows why cephalopods are so keen on RNA editing. Perhaps it is a faster, easier way to adapt to their environment than waiting for a random mutation to occur. Or maybe it better suits their relatively short life spans.
Cephalopods grow up fast and die young . Most live only for a few years and they only breed once. Ragsdale feels RNA editing may help them navigate what are often lonesome, fleeting lives. “This may explain why they’re such good problem solvers. No one’s around to show them how to figure out the world!” Ragsdale says, “How to make their dens. How to camouflage themselves and attack prey. They’re on their own, and fortunately for them they have big brains and can sort matters out.”
Rosenthal feels RNA editing provides cephalopods with another means of environmental flexibility and is planning follow-up research to test his theory: “It can turn certain RNA on and off. We want to see which environmental variables influence the RNA editing process—things like variation in temperature…maybe something more complex like experiences.”
Lore around cephalopods goes back millennia. Aristotle wrote of various forms of “calamari”; seaside cultures have long feared mythic, tentacled beasts like the Norse kraken; Jules Verne, of course, entrenched in us images of a giant squid battling Captain Nemo’s steampunk submarine. And more recently, the squid lent its effort to neuroscience. Much of what we know about how neurons communicate with one another began with experiments in the 1940s and ‘50s on the exceedingly long neuron that runs through the squid body. So perhaps it is fitting that Rosenthal’s new findings suggest cephalopods may hold a unique honor among Earthly species.
Along with fossil records, species are typically dated by analyzing the number of mutations they have accumulated—in most species these genetic blips occur at a steady rate, creating a sort of “molecular clock” that can be used to calculate evolutionary time lines. If RNA editing allows changes in the cephalopod's DNA to occur at a markedly slower rate than is normally assumed, the animals most likely arose many millions of years earlier than current time lines suggest. In other words, the DNA mutations they do harbor would have taken a lot longer to crop up.
“This may mean that our molecular clock estimates of when different cephalopod lineages arose and diverged might be too recent,” Ragsdale says. “The Nobel Prize–winning biologist Sydney Brenner once said that octopi were the first intelligent beings on Earth. This could prove he was right.”