A Casper octopus walks along the seafloor more than 2,300 meters deep near Gardner Pinnacles, northwest of Oahu.
Image credit: Ocean Exploration Trust, NOAA
Octopuses can open jars, solve puzzles, and change color in a split second to match their environment. Scientists have long wondered how a soft-bodied relative of clams and scallops ended up with the largest brain of any invertebrate. A new study from the University of Vienna suggests part of the answer may lie in how octopus DNA is folded inside their cells.
The research, published October 9 in Nature Communications, focused on octopuses, squid, and cuttlefish, which share a common ancestor that lived hundreds of millions of years ago. At some point in that ancestor's history, large sections of its DNA were broken apart and stitched back together in a new order.
DNA does not sit in a cell as a neat, straight strand. It is folded into a tangled three-dimensional structure. Think of a long extension cord coiled up in a drawer: two outlets at opposite ends of the cord can end up side by side. When DNA folds that way, stretches that are far apart on the strand can touch and start influencing how active a gene is.
When the ancient shuffle moved distant pieces of DNA next to each other, over time those connections became woven into larger networks. The researchers call this regulatory entanglement, and they say it may let a species develop new traits while keeping essential biological functions stable.
The team mapped the folded DNA of a bobtail squid, a cuttlefish, and a California two-spot octopus. The broad layout of the DNA stayed largely the same across all three. The smaller connections between distant DNA spots differed widely between species, body tissues, and stages of development, and many sat near genes tied to key cephalopod traits, including the nervous system.
The octopus stood out. Its DNA showed signs of more rearrangement than the squid and cuttlefish, which the authors say created more connections between regions that once sat far apart.
To test whether these DNA changes matter for the brain, the researchers ran an experiment in a relative of the bobtail squid, deleting a roughly 1,000-letter stretch of DNA inside one of those connected regions. All 25 embryos showed developmental delays, but the damage varied. Five had visibly smaller brains, particularly in the optic lobe, and six were smaller overall with shorter arms. Five were severely malformed, and nine showed no obvious defect. Genes millions of DNA letters away from the deletion also changed their activity, which the authors read as a sign that distant parts of the folded genome work together.
The researchers say their findings challenge the view that the shape of a genome is a passive byproduct of evolution. If the folding itself steers what evolution builds, then the octopus’s intelligence may be written partly in the layout of its DNA, and the same may be true for the squid and cuttlefish that share its ancestry.
