A Hawaiian bobtail squid (Euprymna scolopes) rests on a reflective surface
a Hawaiian bobtail squid (Euprymna scolopes) resting on a reflective surface

Reshuffled Genomes May Explain Cephalopods’ Smarts

In two related studies, researchers describe huge chromosomal rearrangements and about 500 novel gene clusters in the octopus, squid, and cuttlefish genomes, which they say could help explain how they evolved their extraordinary brains.

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Sophie Fessl

Sophie Fessl is a freelance science journalist. She has a PhD in developmental neurobiology from King’s College London and a degree in biology from the University of Oxford.

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May 13, 2022

ABOVE: A Hawaiian bobtail squid (Euprymna scolopes) TOM KLEINDINST

Octopuses, squids, and cuttlefish—together referred to as the coleoid, or soft-bodied, cephalopods—are astonishingly clever, dextrous, and ingenious. They problem solve, plan for the future, and have the largest nervous systems among invertebrates. Now, two recent studies with some shared coauthors that were published in Nature Communications on April 21 and May 4, uncover chromosomal restructuring that may explain how the novelties of this curious group evolved. 

Gül Dölen, a neuroscientist at Johns Hopkins University who was not involved in either study, says the studies will help scientists understand how genes, synapses, and circuits produce complex behaviors. “As a neurobiologist interested in understanding brain evolution, I think this is a major step forward.”

Cephalopod genomes reveal large gene rearrangements

In 2015, some of the authors behind the new studies sequenced the first cephalopod genome, that of the California two-spot octopus (Octopus bimaculoides)At that time, the researchers noticed that the animal’s genes appeared to be arranged differently from those of other animals. Usually, “genes stay on the same chromosome,” says Oleg Simakov, a developmental biologist at the University of Vienna in Austria and co-author of the 2015 study as well as both newly published studies. In the California two-spot octopus, though, many genes weren’t in their expected places.

California two-spot octopus (<em>Octopus bimaculoides</em>) in front of a black background
California two-spot octopus (Octopus bimaculoides)

However, the evolutionary significance of this reordering wasn’t clear, and became the subject of the newly published studies. “We wanted to ask: Is there any function?” Simakov recalls. Also, the researchers wanted to make sure that the apparent rearrangement wasn’t an artifact of the methods they used to assemble the genome years earlier. To answer these questions, the researchers needed more detail—specifically, the chromosomal arrangement. “If you don’t have chromosomes, you only have pieces of the genome,” says Hannah Schmidbaur, a former graduate student of Simakov and co-author of the new studies. 

See “What Scientists Learned by Putting Octopuses in MRI Machines

In the May 4 study, the researchers constructed chromosome-level genomes for the California two-spot octopus and two other coleoid cephalopods—the Boston market squid (Doryteuthis (Loligo) pealeii) and the Hawaiian bobtail squid (Euprymna scolopes)—by combining previously reported sequences with ones they obtained with HiC chromatin conformation capture, a method that cross-links nearby sequences to reveal the spatial organization of chromatin. Compared to genomes from some of their mollusk kin, the coleoid cephalopods’ genomes are very divergent, says Simakov. “You have this mosaic of chromosomes, where ancestral chromosomes were broken up and pieces randomly fused to each other, forming new chromosomes.” Even compared to each other, the three genomes are highly rearranged, he notes—a degree of rearrangement that came as a surprise. 

Going into the work, Simakov says some researchers expected that the cephalopods’ genomes would reveal an ancient whole-genome duplication. Schmidbaur notes that a chromosome duplication occurred early on in the evolution of vertebrates and the event is often credited with providing the genetic fodder for the group’s complex brains and other notable traits. But no such duplication occurred in coleoid cephalopods, says Simakov. “There is just one copy of each gene, but the chromosomes were still broken up and have undergone—we don’t know the exact mechanism how—movements,” he says. “By combining different pieces of otherwise preserved ancestral chromosomes, new chromosomes formed.”

Creating new functionality by grouping new genes together

Understanding the evolutionary meaning of all this genetic reorganizing required zooming in on gene order. So, for the other new paper, researchers focused on the order of genes in the Hawaiian bobtail squid genome. They found that genes scattered about in the genomes of other marine invertebrates had come together in specific areas of the squid’s chromosomes, creating roughly 500 new so-called gene blocks, or microsyntenies, says Akane Kawaguchi, a molecular biologist at the Research Institute of Molecular Pathology in Vienna and one of the coauthors of this study. 

See “Octopuses On Ecstasy Reveal Commonalities with Humans

The emergence of these novel gene clusters is related to the large-scale chromosomal rearrangements observed in coleoid cephalopods, says Simakov, as the fusing of previously disparate regions is what created the microsyntenies. And these rearrangements likely affect gene expression, Kawaguchi tells The Scientist. “If three genes are on different chromosomes, their expression is not regulated at the same time or [in the] same tissue,” she notes; however, if they are near one another, their expression could be more coordinated. 

An Atlantic longfin inshore squid  (<em>Doryteuthis pealeii</em>) in shallow water
Atlantic longfin inshore squid (Doryteuthis pealeii)

Indeed, the team found that the new gene clusters affected expression. The researchers looked at a particular group of genes that are spread widely across two chromosomes in the scallop Mizuhopecten yessoensis but are densely packed as a cluster in one chromosome of the Hawaiian bobtail squid. In situ hybridization in the bobtail squid showed that all the genes in this cluster are expressed in the central brain region, but also in tissues and organs where they aren’t expressed in the scallops, such as their gills. “We think that most likely, by bringing these genes together and facilitating a new regulation, they could play a role in the evolution of the nervous system,” says Schmidbaur. 

Simakov admits that the studies “don’t provide the final answer” as to whether these new gene regions are behind the critters’ impressive brains. “We don’t have a proof, but find an association that these genes are active in particular tissues that people know are important for the biology and what contributes to making cephalopods unique.” He sees functional assays as the next big step to studying how microsyntenies affect the animals’ biology and development.

Cephalopods have “all these weird and wonderful ways of increasing their complexity and diversity in ways that vertebrates have never even attempted,” concludes Culum Brown, a biologist at Macquarie University in Australia who was not involved in the study. “It’s a completely unique way of getting to the same kind of results that vertebrates have achieved.” 

Brown finds the microsynteny results “potentially interesting,” and expects that similar results will be seen in other coleoid cephalopods. “It’s not all that surprising that these [gene] families are showing up as unique and popping out of the analysis, but it is kind of cool.” Regardless, he says it’s clear the animals can teach researchers a lot about biology, as they keep “doing these weird things nobody ever thought possible.”