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Only during the past decade have scientists begun to tease apart the mysteries of Hox genes. Clustered in groups of eight to 11, on as many as four chromosomes in a developing embryo's cells, these genes switch on and off in sequence. Since embryos mature from the top down, explains biologist Cliff Tabin of the Harvard Medical School, a Hox gene that turns off a bit early, or stays on just a touch longer, can make a dramatic difference in the formation of the embryo. Swans, for example, have more neck vertebrae than chickens and thus longer necks. That is because the Hox genes responsible for making neck bones stay on longer in the unhatched cygnet than in the unhatched chick.
Timing may also explain the progression of fins to feet. In tetrapods (four-legged animals), feet do not grow straight out of the leg, proceeding from the ankle out, but develop in a fanlike progression that runs from the smallest digit to the largest. In Geneva, Duboule and his colleagues tracked the activity of four Hox genes in the budding feet of embryonic mice and found precisely this pattern. By contrast, studies showed that in the zebrafish, the Hox genes switch off earlier, perhaps to ensure that a flexible fin ray (useful for swimming) will form in the place of feet. Duboule speculates that if these genes could be tricked into staying on just a bit longer, the fins of the zebrafish might sprout appendages suggestive of primitive feet.
What would a fish with feet look like? It could easily resemble the Acanthostega. Mineralized bones of this strange creature, unearthed in Greenland in 1987, tend to confirm the notion that fish did not crawl onto shores on their fins, says paleontologist Michael Coates of University College, London. Instead they probably developed limbs and feet that they used in the water for millions of years before they were capable of colonizing the land.
The transition to land was likely a gradual affair involving multiple stages of evolutionary change. The skeletons of fish, with their slender bones arrayed all in a row, are clearly ill suited for walking and running. Moreover, the muscles of fish are designed to deliver power in all the wrong places. "Think about tucking into a tetrapod [a cow, for instance] for Sunday lunch," says Coates. "The best cuts are the thighs and shoulders, the muscle motors that drive these animals along. In a fish these motors are pathetic, tiny things. It's the back and tail muscles that propel it through the water."
Duboule believes that over the eons of prehistory, Hox genes played a key role in the origin of species, facilitating the process of evolutionary change. Scientists now know, for example, that the genes that trigger the formation of hands and feet also control many other developmental processes in the posterior part of an animal -- among them, the addition of an anal opening to the digestive tract and, in four-legged creatures, the fusion of the lower vertebrae to make a pelvis. Isn't it curious, says Duboule, that fish lack a true pelvis as well as hands and feet? This suggests to him that both structures -- the appendages for walking and the bony apparatus that anchors them to the spine -- are linked at some deep genetic level that is yet to be plumbed.