Squid and octopus genome studies reveal how their elaborate nervous systems evolved

Squid, octopus and cuttlefish are known as soft-bodied or coleoid cephalopods. They have the largest nervous system of any invertebrate, complex behaviours such as instantaneous camouflage, arms studded with dexterous suckers, and other evolutionarily unique traits.

Now, an international team of scientists have dug into the cephalopod genome and discovered it’s just as weird as the animals themselves. These genomes are large, have been scrambled and rearranged dramatically, and contain hundreds of unique genes and unusually expanded gene families.  

Their research has been reported in two new studies published in Nature Communications.

In the first study, the team analysed and compared the genomes of three cephalopod species – two squids (Doryteuthis pealeii and Euprymna scolopes) and an octopus (Octopus bimaculoides). The feat took several years and involved labs from all around the world.

“Large and elaborate brains have evolved a couple of times,” says co-lead author Caroline Albertin, Hibbitt Fellow at the Marine Biology Laboratory (MBL) in the US. “One famous example is the vertebrates.

“Another is the soft-bodied cephalopods, which serve as a separate example for how a large and complicated nervous system can be put together,” she adds. “By understanding the cephalopod genome, we can gain insight into the genes that are important in setting up the nervous system, as well as into neuronal function.”

California two-spot octopuses (Octopus bimaculoides) emerging from their egg casings. Credit: Caroline Albertin/ Marine Biological Laboratory

What’s so striking about cephalopod genomes?

To start with, these genomes are really large. The Doryteuthis genome is 1.5 times larger than the human genome, and the octopus genome is 90% the size of a human’s.

The team identified hundreds of genes in novel gene families that are unique to these organisms, and some of these are highly expressed in unique cephalopod features, including in the squid brain.

Other gene families are unusually expanded (where there are additional gene copies), such as the genes for protocadherins. These are call-adhesion molecules expressed mainly in the nervous system that seem to be involved in both the development and function of the nervous system.

“Cephalopods and vertebrates independently have duplicated their protocadherins, unlike flies and nematodes, which lost this gene family over time,” explains Albertin. “This duplication has resulted in a rich molecular framework that perhaps is involved in the independent evolution of large and complex nervous systems in vertebrates and cephalopods.”

They also followed up on previous research that showed squid and octopus displaying an extraordinarily high rate of RNA editing – editing of the RNA messengers that carry instructions from DNA for controlling the synthesis of proteins.

RNA editing diversifies the kinds of proteins that the animal can produce, and they found in Doryteuthis that this phenomenon is restricted to the nervous system.

The Atlantic longfin inshore squid, Doryteuthis pealeii, has been studied for nearly a century by scientists as a model system for neuroscience investigations.

But most strikingly, according to Albertin, is that the cephalopod genome “is incredibly churned up”.

As if the ancestral genomes were put into a blender, all three cephalopod genomes have seen immense genome rearrangements and are highly rearranged relative to each other (as well as compared to other animals).

“In many animals, gene order within the genome has been preserved over evolutionary time,” says Albertin. “But in cephalopods, the genome has gone through bursts of restructuring.

“This presents an interesting situation: genes are put into new locations in the genome, with new regulatory elements driving the genes’ expression. That might create opportunities for novel traits to evolve.”

In a second study, published last week, the team explored how the highly reorganised genome in Euprymna scolopes affects gene expression. They found that the genome rearrangements resulted in new gene interactions that may be involved in making many of the novel cephalopod tissues, including their large, elaborate nervous systems.


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