Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body

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Authors: Neil Shubin
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and this result is coupled with a duplication of the bones. Randy injected the egg, waited a day or so, and then checked whether, as in chickens, the vitamin A caused Sonic hedgehog to turn on in the opposite side of the limb. It did. Now came the long wait. We knew that Sonic hedgehog was behaving the same way in our hands and in skates’ and sharks’ fins. But what would the effect of all this be on the skeleton? We would have to wait two months for the answer.
    The embryos were developing inside an opaque egg case. All we could tell was whether the creature was alive; the inside of the fin was invisible to us.
    The end result was a stunning example of similarity among us, sharks, and skates: a mirror-image fin. The dorsal fins duplicated their structures in a wonderful front-to-back pattern, the same kind we saw with experiments in limbs. Limbs duplicate a limb structure. Shark fins duplicate a shark fin structure as do skates. Sonic hedgehog has a similar effect in even the most different kinds of appendage skeletons found on earth today.
    One effect of Sonic hedgehog, you may recall, is to make the fingers distinct from one another. As we saw with respect to the ZPA, what kind of digit develops depends on how close the digit is to the source of Sonic hedgehog. A normal adult skate fin contains many skeletal rods, which all look alike. Could we make these rods different from one another, like our digits? Randy took a small bead impregnated with the protein made by Sonic hedgehog and put it in between these identical skeletal rods. The key to his experiment is that he used mouse Sonic hedgehog. So now we have a real contraption: a skate embryo with a bead inside that is gradually leaking mouse Sonic hedgehog protein. Would that mouse protein have any effect on a shark or a skate?
    There are two extreme outcomes to an experiment like this. One is that nothing happens. This would mean that skates are so different from mice that Sonic hedgehog protein has no effect. The other extreme outcome would present a stunning example of our inner fish. This outcome would be that the rods develop differently from one another, demonstrating that Sonic hedgehog does something similar in skates and in us. And let’s not forget that since Randy is using the protein from a mammal, it means that the genetic recipe would be really, really similar.
    Not only did the rods end up looking different from one another, they responded to Sonic hedgehog, much as fingers do, on the basis of how close they were to the Sonic hedgehog bead: the closer rods developed a different shape from the ones farther away. To top matters off, it was the mouse protein that did the job so effectively in the skates.
     

Normal fins (left) and Randy’s treated fins. The treated fins showed a mirror-image duplication just as chicken wings did. Photographs courtesy of Randall Dahn, University of Chicago.
     
    The “inner fish” that Randy found was not a single bone, or even a section of the skeleton. Randy’s inner fish lay in the biological tools that actually build fins. Experiment after experiment on creatures as different as mice, sharks, and flies shows us that the lessons of Sonic hedgehog are very general. All appendages, whether they are fins or limbs, are built by similar kinds of genes. What does this mean for the problem we looked at in the first two chapters—the transition of fish fins into limbs? It means that this great evolutionary transformation did not involve the origin of new DNA: much of the shift likely involved using ancient genes, such as those involved in shark fin development, in new ways to make limbs with fingers and toes.
    But there is a deeper beauty to these experiments on limbs and fins. Tabin’s lab used work in flies to find a gene in chickens that tells us about human birth defects. Randy used the Tabin lab discovery to tell us something about our connections to skates. An “inner fly” helped find an “inner chicken,” which

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