About 360 million years ago, as any schoolchild who knows his prehistoric zoology can tell you, some adventurous fish managed to hoist themselves onto their stubby fins and crawl clumsily out of the swamps to forage for food. Once these primeval creatures were on terra firma, their offspring began to adapt to their new environment, natural selection (over tens of millions of years) favoring those that developed features well suited to life on land: paws, hooves, knees, joints, fingers and thumbs. Thus, as generations of schoolchildren have learned, did these marine creatures give rise to frogs, birds, dinosaurs and all the rest.
There's one problem with this familiar version of how our distant ancestors emerged from the sea: it's probably wrong. For one thing, newly assembled fossils -- in particular, a 360 million-year-old salamander-like aquatic animal called Acanthostega -- strongly suggest that toes and feet were developed before life climbed onto land, not after. Moreover, in shape and function, Acanthostega's fully jointed toes bear no resemblance to the spiky, fanlike fins of a fish. Scientists believe they understand how a fish's gills evolved into an amphibian's lungs. But how did fins turn into feet like these?
The answer may be in the genes. That's the tantalizing conclusion of a team of researchers from the University of Geneva in Switzerland. They have discovered that genes associated with the formation of fins in fish are the same ones that orchestrate the development of paws in mice. "Think of a mouse as a fish with limbs, or a fish as a mouse with fins," says University of Geneva developmental biologist Denis Duboule. "What a mouse does is take a fin and put something extra on top of it."
That something extra, Duboule and his colleagues suggest in the journal Nature, is provided by a special set of genes that act as master architects in a surprisingly broad range of animals, from rodents to roundworms. These gossamer strands of DNA -- known as homoeotic homeobox genes, or Hox genes for short -- lay out the embryo from head to tail, controlling everything from the development of limbs and the wiring of the spinal cord to the patterning of the gut and urogenital tracts. "What's amazing," says University of Pennsylvania paleontologist Neil Shubin, "is that evolution of complex structures appears to be controlled by this same small set of genes."
How do Hox genes pack such power? The DNA in all genes carries instructions for assembling proteins out of chemical building blocks called amino acids. What sets the proteins made by Hox genes apart is the biochemical motif known as a homeobox, a stylized string of 60 amino acids that enables Hox proteins to stick to DNA like strips of molecular Velcro and, in the process, activate still other genes. Hundreds of genes belong to the extended homeobox family, but those that are also homoeotic -- associated with changes in body parts -- are the most important. Though they are few in number (38 out of an estimated 50,000 to 100,000 genes in modern vertebrates), the Hox genes control much of what happens during embryonic development.