The cuttlefish and its relatives, squid and octopuses, often strike human observers as floating aliens wreathed in sucker-covered limbs — boneless, squirming appendages that would seem to have nothing in common with our own arms and legs.
But hidden under the superficial differences, a new study shows, are some profound similarities: Human and cuttlefish limbs develop under the direction of the same genes. The new study, published on Tuesday in the journal eLife, lends weight to the theory that many animal appendages, from insect wings to fish fins, share a long evolutionary history.
Cuttlefish, squid and octopuses are all cephalopods, a group that evolved over 400 million years ago from a mollusk ancestor. Later, cephalopods evolved appendages in two forms.
An octopus has eight appendages, each of which has rows of suckers running its length. But these are not tentacles — in strict anatomical terms, they are arms. A tentacle has suckers only on its pad-shaped ending. Squid and cuttlefish have arms, but also tentacles.
Cephalopod tentacles and arms lack bones; instead, they are built from an intricate tapestry of coiling muscle fibers. A cuttlefish shoots a tentacle at its prey by contracting fibers along the tentacle’s entire length. By contracting only some fibers, an octopus can work its arms into a tiny recess or, famously, unscrew the lid from a jar.
Martin Cohn, an evolutionary biologist at the University of Florida and a co-author of the new study, has long wondered how cephalopod limbs evolved, given that their mollusk ancestors had none. A few years ago, he tackled this question by observing how cuttlefish develop from eggs.
This is no easy task, because female cuttlefish lay their eggs inside a tough capsule. Oscar Tarazona, a graduate student working with Dr. Cohn, figured out how to coax individual eggs out of the capsule without rupturing them.
He gently placed them in a petri dish loaded with nutrients, and the scientists watched the embryos take shape and sprout limbs. By adding colored proteins, the researchers determined when particular genes became active in particular parts of the cephalopod embryo.
Early in development, a set of genes becomes active in each limb, Dr. Cohn and his colleagues found. Some genes are active in the cells near the cuttlefish’s body, but less so at the tip. Some are active in one side of a limb but not the other.
These genes seemed to be organizing the developing limb, telling each cell about its location. That information might lead the cells to evolve into the right tissues for their spots in the limb.
To test this hypothesis, the researchers ran a series of experiments.
Normally, the tentacles only grow suckers on one side of their pads. The scientists treated the other side with a chemical that interfered with one of the genes. As Dr. Cohn had predicted, the cuttlefish then grew suckers on the wrong side.
“Cells have to interpret where they are,” he said. “These signals are telling cells, ‘You’re close to the end of this appendage, you’re furthest from the edge, you’re sitting in the middle.’”
Vertebrates, too, produce signals in developing limbs that tell cells where they are. These signals can mark an arm or a leg in three dimensions. Remarkably, these are the same genes at work in cuttlefish.
In the 1990s, researchers found that flies use these genes to build their limbs. In an influential paper, Neil Shubin of the University of Chicago, Sean Carroll of the University of Wisconsin-Madison and Cliff Tabin of Harvard University speculated that flies and vertebrates — and other animals with appendages — inherited this network of genes from a common ancestor.
The challenges of tracking genes in embryos slowed the exploration of this provocative idea. Now, more than twenty years later, Dr. Cohn and his colleagues have found this genetic network active in animals far removed from vertebrates or insects.
“The limbs of flies, cephalopods and people came about independently over the past 500 million years — not only by using the same genes, but by deploying them in similar ways to make outgrowths of the body,” said Dr. Shubin, who was not involved in the new study.
It’s possible that the common ancestor of cuttlefish, flies and humans had limbs of some sort. Perhaps the animal used these genes to map the coordinates in other three-dimensional body parts, even one located entirely inside the body.
In later generations, animal lineages evolved profound differences. When it comes to limbs, flies and other insects are as different from cephalopods as they are from us. They have hard exoskeletons, with muscles pulling on them from the inside.
But every time a new kind of limb evolved, it seems, animals did not need a new way to tell cells where they were located inside it. Evolution reused the same genetic program over and over again.
“We’re looking at something ancient,” Dr. Cohn said.