The octopus, the shuffled genome and the clever brain
A simple, illustrated story of a new study showing how the folding of DNA may have helped octopuses, squid and cuttlefish evolve clever brains. With key terms and an easy quiz.
Zoology Student Hub
10/12/20267 min read
Who's who. The new study looked at one squid, one cuttlefish and one octopus. Nautilus is their shelled cousin.
1. Meet the cleverest animals without a backbone
Picture an octopus in an aquarium. It unscrews the lid of a jar to reach a crab inside. It squeezes its soft body through a gap no wider than its beak. It changes colour in a blink to match a rock. For an animal that is a close cousin of snails and clams, that is remarkable.
Octopuses, squid and cuttlefish belong to a group of molluscs called cephalopods (meaning "head-foot", because their arms grow from the head). The ones we are talking about today, which have lost or hidden their shells, are called coleoids. Their only shelled living relative is the Nautilus, which still carries a coiled shell on its back.
Here is the puzzle. Our brains and the octopus brain evolved separately. Our last shared ancestor, more than half a billion years ago, was a small, simple creature with no brain worth the name. So how did octopuses end up so clever? A team of scientists at the University of Vienna went looking for clues in an unexpected place: the way DNA is folded inside their cells.
Packing DNA. Thread → beads on a string → loops grouped into neighbourhoods. Scientists call the bigger neighbourhoods chromatin domains (or TADs).
2. DNA is a very long thread in a very small box
Every cell keeps its DNA in the nucleus. If you pulled the DNA out of one of your cells and stretched it, it would be about two metres long. The nucleus is a few thousandths of a millimetre wide. That is like stuffing about 20 km of fine thread into a tennis ball.
The cell manages this by packing neatly. First, DNA winds around little protein spools called histones, making "beads on a string" (each bead is a nucleosome). Then the string bunches into loops, and loops gather into neighbourhoods. The whole packed material is called chromatin.
Packing is not random. It decides which parts of the DNA can "talk" to each other, and that turns out to matter a lot.
Switch and bulb. An enhancer (switch) can control a gene (bulb) only when a chromatin loop brings them close together in 3D space.
3. Why folding matters: switches and light bulbs
A gene is a stretch of DNA that carries instructions for making something, usually a protein. But a gene does not switch itself on. It needs a switch, a short piece of DNA called an enhancer.
The surprising part: the switch can sit very far from its gene along the thread, sometimes a million letters away. So how does the switch reach the light bulb? The DNA folds into a loop, and the loop brings the switch right next to the gene. No loop, no contact. No contact, no light.
Think of it like this: a library where a book's index card is kept on a different floor. Folding the building so the two floors touch lets you find the book. Folding is how the genome connects distant parts.
Shuffling makes new neighbours. A simplified picture of the idea in the study. The gene and switch shown are made-up examples to explain the principle.
4. The twist in the octopus story: a shuffled pack of cards
In most animals, genes stay in roughly the same order on their chromosomes for hundreds of millions of years. Scientists call this kept order synteny. You, a fish and a sea anemone still share many of the same gene neighbourhoods.
Coleoids are different. Long ago, in their ancestors, chromosomes joined together and then got mixed up, like two packs of cards stuck together and shuffled. Genes and switches that used to live on separate chromosomes suddenly became neighbours. The study found this shuffling was especially strong in the octopus line.
New neighbours can form new loops. A switch that once sat on a different chromosome can now reach a gene and turn it on in a new place or at a new time, for example in a new part of the brain.
The toolkit. Putting the three maps side by side shows which folds bring which switches to which active genes.
5. What the scientists did and what they found
The team, led by Thea Rogers at the University of Vienna, studied embryos and tissues of the Hawaiian bobtail squid (Euprymna scolopes), the common cuttlefish (Sepia officinalis) and the California two-spot octopus (Octopus bimaculoides). They made three kinds of DNA "maps": Micro-C (who is touching whom?), ATAC-seq (which doors are open?) and RNA-seq (which genes are ON?).
Here is what they found, in plain words:
The big neighbourhoods stayed the same. The large chromatin domains looked broadly similar in squid, cuttlefish and octopus.
The small loops kept changing. Hundreds of loops were found in only one species, or only at one stage of development, and many sat near genes connected to the nervous system.
The loops do real work. Using CRISPR gene editing, the team removed one suspected switch inside a conserved region and saw effects on how the nervous system develops.
The authors call the slow build-up of these new links "regulatory entanglement": over millions of years, genes and switches become so connected that they stay together, and the animal gains new ways to control its genes without breaking the old ones.
A fair note: this is a strong idea backed by good evidence, but it does not yet prove that a particular loop made the octopus clever. Science moves step by step, and this is one important step.
6. The big lesson
We often think evolution works by changing genes. This study is a reminder that where a gene sits and who its neighbours are can matter just as much. In octopuses, an ancient shuffle of chromosomes, followed by new folds, may have given evolution fresh material to build a remarkable brain.
Important notes: key terms in simple words
DNA: the molecule that stores genetic instructions, made of two strands twisted into a double helix.
Gene: a stretch of DNA that carries instructions for making a product, usually a protein.
Chromosome: one long DNA molecule packed with proteins. Humans have 46 in most body cells.
Histone and nucleosome: histones are proteins that act like spools. DNA wrapped around a group of histones is a nucleosome, the "bead" in "beads on a string".
Chromatin: DNA plus its packing proteins. Loose chromatin is easy to read; tightly packed chromatin is usually silent.
Enhancer: a short DNA "switch" that boosts a gene's activity, even from far away, once a loop brings it close.
Chromatin loop: a fold that brings two distant pieces of DNA into contact, such as an enhancer and its gene.
Chromatin domain (TAD): a larger "neighbourhood" of DNA whose parts touch each other more than they touch the outside.
Synteny: genes staying in the same order or on the same chromosome across different species.
Cephalopod / Coleoid: cephalopods are molluscs with arms on the head. Coleoids are the ones with no outer shell: squid, cuttlefish, octopus.
CRISPR–Cas9: a gene-editing tool that cuts DNA at a chosen spot, letting scientists remove or change a sequence to test what it does.
Remember these points
DNA is packed in levels: DNA → nucleosomes → loops → domains.
Folding decides which switches can reach which genes.
Octopus, squid and cuttlefish chromosomes were joined and shuffled long ago, creating new gene neighbours.
Big domains were similar across the three animals; small loops varied a lot.
Many changing loops sit near nervous-system genes, linking genome folding to brain evolution.
Quick quiz: test your terms
Try them first, then check the answers below.
DNA wrapped around histone proteins forms a: (a) ribosome (b) nucleosome (c) lysosome (d) centrosome
A short piece of DNA that acts like a switch to boost a gene's activity is called an: (a) enhancer (b) exon (c) enzyme (d) episome
Which of these is NOT a coleoid? (a) octopus (b) squid (c) Nautilus (d) cuttlefish
Cephalopods belong to which animal phylum? (a) Arthropoda (b) Echinodermata (c) Mollusca (d) Chordata
True or false: an enhancer must sit right next to its gene on the DNA thread to work.
Fill in the blank: DNA together with its packing proteins is called ________.
Genes staying in the same order on chromosomes across different species is called: (a) mutation (b) synteny (c) symbiosis (d) transcription
In this study, which part of genome folding changed the most between squid, cuttlefish and octopus? (a) the large chromatin domains (b) the small chromatin loops (c) the DNA double helix itself (d) the number of histones
Which tool did the scientists use to remove a DNA switch and test what it does? (a) PCR (b) CRISPR–Cas9 (c) gel electrophoresis (d) microscopy
RNA-seq answers which question? (a) "Who is touching whom?" (b) "Which doors are open?" (c) "Which genes are ON?"
Answers
1 (b) nucleosome · 2 (a) enhancer · 3 (c) Nautilus, it still has a hard outer shell · 4 (c) Mollusca · 5 False, a loop brings it close · 6 chromatin · 7 (b) synteny · 8 (b) the small chromatin loops · 9 (b) CRISPR–Cas9 · 10 (c) "Which genes are ON?"
Sources
Rogers, T. F. et al. (2026). Genome reorganisation and expansion shape 3D genome architecture and define a distinct regulatory landscape in coleoid cephalopods. Nature Communications 17, 10319. Published 9 October 2026. doi.org/10.1038/s41467-026-77625-7
University of Vienna press release (9 October 2026): 3D structure of DNA may explain how cephalopods evolved complex brains
EurekAlert! version of the release: eurekalert.org/news-releases/1146777
The diagrams in this post were drawn for Zoology Student Hub as simplified teaching illustrations; they are not figures from the paper.
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