Octopus genome sequenced

The California Two-Spot Octopus, the first octopus genome to be sequenced. Credit: Judit Pungor/Nature.

The California Two-Spot Octopus, the first octopus genome to be sequenced. Credit: Judit Pungor/Nature.

We here at Science Life try to avoid editorializing, but we can’t help ourselves this time. Octopuses are really, really cool. And weird. A few octopus facts:

  • They’re cephalopods, a group of predatory mollusks that include squids and cuttlefish.
  • They’re incredibly intelligent (more accurately, they demonstrate complex problem-solving and learning behaviors).
  • They have big, complex nervous systems with a donut-shaped brain that runs around their esophagus. Also they have three hearts.
  • They’re ancient. Cephalopods evolved more than 500 million years ago. That’s before plants moved on to land.
  • They have eight prehensile tentacles, lined with rows of suckers that can taste, innervated by what is essentially a second central nervous system. These tentacles can be completely regenerated if lost.
  • They have vertebrate-like eyes, one of the most striking examples of convergent evolution known.
  • They inhabit every ocean, at every depth, and range in size from really tiny to giant.
  • They can predict the future (Okay, fine, this one is still up for debate).
  • And maybe coolest of all, they have the most sophisticated adaptive camouflage system in the animal kingdom – they can change color, texture, shape, etc., almost instantaneously.

These specialized octopus traits, especially their complex nervous systems, are what’s drawn the interest of Clifton Ragsdale, PhD, associate professor in the in the Departments of Neurobiology and Organismal Biology and Anatomy. Because octopuses are about as distantly related to humans as is evolutionary possible, they represent an ideal system for Ragsdale, a neurobiologist whose research focuses on understanding how brains develop, to explore how nature creates a large and sophisticated brain.

Clifton Ragsdale, PhD, associate professor of neurobiology and organismal biology and anatomy

Clifton Ragsdale, PhD

To tackle this question, Ragsdale and his colleagues needed to better understand the genetics that underlie octopus traits. So they sequenced the genome of the California two-spot octopus (Octopus bimaculoides), the first cephalopod ever to be fully sequenced. What did they find? A gigantic genome that possesses striking differences from other invertebrates, including a dramatic expansion of a gene family involved in neuronal development that was once thought to be unique to vertebrates. They published their findings in Nature on Aug 12, 2015.

“The octopus appears to be utterly different from all other animals, even other molluscs, with its eight prehensile arms, its large brain and its clever problem-solving capabilities,” said Ragsdale, who is co-senior author on the study. “The late British zoologist Martin Wells said the octopus is an alien. In this sense, then, our paper describes the first sequenced genome from an alien.”

Short-range brain

Ragsdale and his colleagues, including teams from University of California, Berkeley and Okinawa Institute of Science and Technology as part of the Cephalopod Sequencing Consortium, sequenced the O. bimaculoides genome to a high level of coverage (on average, each base pair was sequenced 60 times). To annotate it, they generated transcriptome sequence data – which can be used to measure gene expression based on RNA levels – in 12 different tissues types.

The team estimate the O. bimaculoides genome is 2.7 billion base-pairs in size, with numerous long stretches of repeated sequences. They identified more than 33,000 protein-coding genes, placing the octopus genome at slightly smaller in size, but with more genes, than a human genome.

The large size of the octopus genome was initially attributed to whole genome duplication events during evolution, which can lead to increased genomic diversity and complexity. This phenomenon has occurred twice in ancestral vertebrates, for example. However, Ragsdale and his colleagues found no evidence of duplications.

Instead, the evolution of the octopus genome was likely driven by the expansion of a few specific gene families, widespread genome shuffling and the appearance of novel genes.

The most notable expansion was in the protocadherins, a family of genes that regulate neuronal development and short-range interactions between neurons. The octopus genome contains 168 protocadherin genes – 10 times more than other invertebrates and more than twice as many as mammals. It was previously thought that only vertebrates possessed numerous and diverse protocadherin genes. The research team hypothesized that because cephalopod neurons lack myelin and function poorly over long distances, protocadherins were central to the evolution of a nervous system whose complexity depends on short-range interactions.

Other gene families that were dramatically expanded in the octopus include zinc finger transcription factors, which are mainly expressed in embryonic and nervous tissues and are thought to play roles in development. The octopus genome contains around 1,800 C2H2 zinc finger transcription factors, the second largest gene family so far discovered in animals (olfactory receptor genes in elephants are the largest at around 2,000).

Overall, however, gene family sizes in octopuses are largely similar to those found in other invertebrates.

A “Cuisinart” genome

A unique feature of the octopus genome appears to be widespread genomic rearrangements. In most species, specific cohorts of genes tend to be close together on the chromosome. However, most octopus genes show no such connections. Hox genes, for example, control body plan development and cluster together in almost all animals. Octopus Hox genes are scattered throughout the genome with no apparent linkages.

The octopus genome is enriched in transposons, also known as “jumping genes,” which can rearrange themselves on the genome. While their role in octopuses is unclear, the team found elevated transposon expression in neural tissues. Transposons are known to affect the regulation of gene expression and play major roles in shaping genome structure.

Carolin Albertin, graduate student in organismal biology and anatomy

Caroline Albertin, graduate student in organismal biology and anatomy

“With a few notable exceptions, the octopus basically has a normal invertebrate genome that’s just been completely rearranged, like it’s been put into a blender and mixed,” said Caroline Albertin, co-lead author and graduate student in the Department of Organismal Biology and Anatomy at the University of Chicago. “This leads to genes being placed in new genomic environments with different regulatory elements, and was a completely unexpected finding.”

The researchers also found evidence of extensive RNA editing, which allows the octopus to alter protein sequences without changing underlying DNA code. Many edited proteins are found in neural tissues, and these proteins are thought to act as a switch to regulate functions such as neural activity.

Hundreds of octopus-specific genes were identified, large numbers of which were found in the nervous system, retina and suckers. The team noted several specific gene families of interest. The suckers, for example, express a set of genes that resemble receptors for the neurotransmitter acetylcholine. However, the proteins these genes code for lack the ability to bind acetylcholine, and are suspected to function as chemosensory receptors involved in the octopus’s ability to taste with their suckers.

Six octopus-specific reflectins, genes involved in light manipulation and camouflage, were identified. Octopus reflectins are relatively dissimilar to reflectins in other cephalopods, suggesting that a single gene was present in a cephalopod ancestor, which then duplicated and evolved independently in different species. This is consistent with the team’s estimates that the octopus and squid lineages diverged around 270 million years ago.

Albertin and Ragsdale are now studying the molecular and genetic mechanisms responsible for the development of the octopus, particularly its brain. Efforts to sequence the genomes of other cephalopods are currently underway through the Cephalopod Sequencing Consortium.

“The octopus genome makes studies of cephalopod traits much more tractable, and now represents an important point on the tree of life for comparative evolutionary studies,” Ragsdale said. “It is an incredible resource that opens up new questions that could not have been asked before about these remarkable animals.”


The study, “The octopus genome and the evolution of cephalopod neural and morphological novelties,” was supported by the National Science Foundation, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, the University of Chicago Institute for Translational Medicine (ITM), and the Molecular Genetics Unit of the Okinawa Institute of Science and Technology Graduate University. Additional authors include Oleg Simakov, Therese Mitros, Z. Yan Wang, Judit R. Pungor, Eric Edsinger-Gonzales, Sydney Brenner and Dan Rokhsar.

About Kevin Jiang (147 Articles)
Kevin Jiang is a Science Writer and Media Relations Specialist at the University of Chicago Medicine. He focuses on neuroscience and neurosurgery, orthopedics, psychology, genetics, biology, evolution, biomedical and basic science research.
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