The elusive octopus genome has finally been untangled, which should allow scientists to discover answers to long-mysterious questions about the animal's alienlike physiology: How does it camouflage itself so expertly? How does it control—and regenerate—those eight flexible arms and thousands of suckers? And, most vexing: How did a relative of the snail get to be so incredibly smart—able to learn quickly, solve puzzles and even use tools?

The findings, published today in Nature, reveal a vast, unexplored landscape full of novel genes, unlikely rearrangements—and some evolutionary solutions that look remarkably similar to those found in humans. (Scientific American is part of Nature Publishing Group.)

With the largest-known genome in the invertebrate world—similar in size to that of a house cat (2.7 billion base pairs) and with more genes (33,000) than humans (20,000 to 25,000)—the octopus sequence has long been known to be large and confusing. Even without a genetic map, these animals and their cephalopod cousins (squids, cuttlefishes and nautiluses) have been common subjects for neurobiology and pharmacology research. But a sequence for this group of mollusks has been "sorely needed," says Annie Lindgren, a cephalopod researcher at Portland State University who was not involved in the new research. "Think about trying to assemble a puzzle, picture side down," she says of octopus research to date. "A genome gives us a picture to work with."

Among the biggest surprises contained within the genome—eliciting exclamation point–ridden e-mails from cephalopod researchers—is that octopuses possess a large group of familiar genes that are involved in developing a complex neural network and have been found to be enriched in other animals, such as mammals, with substantial processing power. Known as protocadherin genes, they "were previously thought to be expanded only in vertebrates," says Clifton Ragsdale, an associate professor of neurobiology at the University of Chicago and a co-author of the new paper. Such genes join the list of independently evolved features we share with octopuses—including camera-type eyes (with a lens, iris and retina), closed circulatory systems and large brains.

Having followed such a vastly different evolutionary path to intelligence, however, the octopus nervous system is an especially rich subject for study. "For neurobiologists, it's intriguing to understand how a completely distinct group has developed big, complex brains," says Joshua Rosenthal of the University of Puerto Rico's Institute of Neurobiology. "Now with this paper, we can better understand the molecular underpinnings."

Part of octopuses' sophisticated wiring system—which extends beyond the brain and is largely distributed throughout the body—controls their blink-of-an-eye camouflage. Researchers have been unsure how octopuses orchestrate their chromatophores, the pigment-filled sacs that expand and contract in milliseconds to alter their overall color and patterning. But with the sequenced genome in hand, scientists can now learn more about how this flashy system works—an enticing insight for neuroscientists and engineers alike.

Also contained in the octopus genome (represented by the California two-spot octopus, Octopus bimaculoides) are numerous previously unknown genes—including novel ones that help the octopus "taste" with its suckers. Researchers can also now peer deeper into the past of this rarely fossilized animal's evolutionary history—even beyond their divergence with squid some 270 million years ago. In all of that time octopuses have become adept at tweaking their own genetic codes (known as RNA editing, which occurs in humans and other animals but at an extreme rate in octopuses), helping them keep nerves firing on cue at extreme temperatures. The new genetic analysis also found genes that can move around on the genome (known as transposons), which might play a role in boosting learning and memory.

One thing not found in the octopus genome, however, is evidence that its code had undergone wholesale duplication (as the genome of vertebrates had, which allowed the extra genes to acquire new functions). This was a surprise to researchers who had long marveled at the octopus's complexity—and repeatedly stumbled over large amounts of repeated genetic code in earlier research.

The size of the octopus genome, combined with the large number of repeating sequences and, as Ragsdale describes, a "bizarre lack of interest from many genomicists," made the task a challenging one. He was among the dozens of researchers who banded together in early 2012 to form the Cephalopod Sequencing Consortium, "to address the pressing need for genome sequencing of cephalopod mollusks," as they noted in a white paper published later that year in Standards in Genomic Sciences.

The full octopus genome promises to make a splash in fields stretching from neurobiology to evolution to engineering. "This is such an exciting paper and a really significant step forward," says Lindgren, who studies relationships among octopuses, which have evolved to inhabit all of the world's oceans—from warm tidal shallows to the freezing Antarctic depths. For her and other cephalopod scientists, "having a whole genome is like suddenly getting a key to the biggest library in the world that previously you could only look into by peeking through partially blocked windows."

Katherine Harmon Courage is a contributing editor for Scientific American and author of the book Octopus! The Most Mysterious Creature in the Sea. Follow her on Twitter @KHCourage.