As many mysteries as the octopus holds—its comprehensive camouflage, smart suckers, agile brain—its genome is surely holding many more (including how it can regenerate its arms—suckers, nerves and all).

"It is astonishing that with the explosion of genome resources for so many life forms, there is not yet available a single assembled cephalopod genome," wrote an international consortium of twenty-eight researchers in a 2012 paper outlining the issue.

So the group set out to solve that problem. They created the Cephalopod Sequencing Consortium ("CephSeq"), which is working to sequence the genomes of 10 cephalopod species, including the well-studied common octopus (Octopus vulgaris), the lab model California two-spot octopus (O. bimaculoides) and the highly venomous blue-ringed octopus (Hapalochlaena maculosa)—along with species of squid, cuttlefish and nautilus. One group in particular is working hard on the California two-spot octopus and hopes to have the draft genome published soon.

But octopus genomes turn out not to be the easiest codes to crack. "Cephalopod genomes are large, complex and full of repeats," the authors noted. The estimated sizes of some of the species' genomes exceed that of the human genome. The California two-spot octopus, for example, is expected to have a genome of about 3.2 billion base pairs—the same size as ours. And blue-ringed octopus is expected to top out at an impressive 4.5 billion base pairs. (By contrast, our furry vertebrate friend the common house mouse has a genome of about 2.7 billion base pairs.) The latest sequencing technology is finally coming up to speed enough to tackle the challenge.

Why dive into such a dark, dense and confusing realm? "Cephalopods are important to science, including the fields of cellular neurobiology, learning and memory, neuroethology, biomaterial engineering, animal-microbe interactions, developmental biology, and fundamental molecular biology such as RNA editing," the researchers wrote. Indeed, although RNA editing was discovered in mammals, octopuses edit their RNA at an astoundingly high rate—precisely why and how, however, we have yet to find out.

Additionally, "access to genomic information will greatly facilitate this ongoing research, particularly through gene discovery," the researchers noted. "Cephalopod genomics will also drive the creation of new areas of investigation, including such biomedically important topics as regeneration and aging." A forthcoming meeting, for example, includes a paper highlighting the use of genetics for discovering potential new natural compounds from a blue-ringed octopus's Pseudoalteromonas bacterium. And other recent research is applying quick DNA barcoding to different octopus species—particularly those of interest for fisheries and burgeoning aquaculture operations.

Octopuses come from one of the most diverse animal phylum on Earth: mollusks. Piecing together the cephalopod genome will help researchers learn how the cephalopods evolved to be so different from their more humble snail and clam cousins. It will also help to reveal the many surprising elements of octopuses' convergent evolution, including their advanced cardiovascular systems, highly differentiated brains and mammal-like eyes.

Additionally, comprehensive genome sequencing will help to bring cephalopods into the scientific spotlight as true model organisms (think rats, fruit flies, etc.)—a development that will also call for further debate about how to ethically study these intelligent invertebrates.

Finally, genetic information will allow researchers to better monitor octopus populations—particularly as they are impacted by fishing, aquaculture and climate change. As research published earlier this year highlighted, shape-shifting, region-varying octopuses are exceedingly difficult to classify based on physical characteristics alone. So a genetic guidebook will be a welcome addition to understanding these strange animals a little bit better.

For more about the insides and outsides of the octopus—including its strange and revealing RNA editing talents—check out Octopus! The Most Mysterious Creature In the Sea, now also out in paperback!

Illustration courtesy of Ivan Phillipsen