Handy Genes
w hile my colleagues and I were digging up the first Tiktaalik in the Arctic in July 2004, Randy Dahn, a researcher in my laboratory, was sweating it out on the South Side of Chicago doing genetic experiments on the embryos of sharks and skates, cousins of stingrays. You've probably seen small black egg cases, known as mermaid's purses, on the beach. Inside the purse once lay an egg with yolk, which developed into an embryonic skate or ray. Over the years, Randy has spent hundreds of hours experimenting with the embryos inside these egg cases, often working well past midnight. During the fateful summer of 2004, Randy was taking these cases and injecting a molecular version of vitamin A into the eggs. After that he would let the eggs develop for several months until they hatched.
His experiments may seem to be a bizarre way to spend the better part of a year, let alone for a young scientist to launch a promising scientific career. Why sharks? Why a form of vitamin A?
To make sense of these experiments, we need to step back and look at what we hope they might explain. What we are really getting at in this chapter is the recipe, written in our DNA, that builds our bodies from a single egg. When sperm fertilizes an egg, that fertilized egg does not contain a tiny hand, for instance. The hand is built from the information contained in that single cell. This takes us to a very profound problem. It is one thing to compare the bones of our hands with the bones in fish fins. What happens if you compare the genetic recipe that builds our hands with the recipe that builds a fish's fin? To find answers to this question, just like Randy, we will follow a trail of discovery that takes us from our hands to the fins of sharks and even to the wings of flies.
As we've seen, when we discover creatures that reveal different and often simpler versions of our bodies inside their own, a wonderfully direct window opens into the distant past. But there is a big limitation to working with fossils. We cannot do experiments on long-dead animals. Experiments are great because we can actually manipulate something to see the results. For this reason, my laboratory is split directly in two: half is devoted to fossils, the other half to embryos and DNA. Life in my lab can be schizophrenic. The locked cabinet that holds Tiktaalik specimens is adjacent to the freezer containing our precious DNA samples.
Experiments with DNA have enormous potential to reveal inner fish. What if you could do an experiment in which you treated the embryo of a fish with various chemicals and actually changed its body, making part of its fin look like a hand? What if you could show that the genes that build a fish's fin are virtually the same as those that build our hands?
We begin with an apparent puzzle. Our body is made up of hundreds of different kinds of cells. This cellular diversity gives our tissues and organs their distinct shapes and functions. The cells that make our bones, nerves, guts, and so on look and behave entirely differently. Despite these differences, there is a deep similarity among every cell inside our bodies: all of them contain exactly the same DNA. If DNA contains the information to build our bodies, tissues, and organs, how is it that cells as different as those found in muscle, nerve, and bone contain the same DNA?
The answer lies in understanding what pieces of DNA (the genes) are actually turned on in every cell. A skin cell is different from a neuron because different genes are active in each cell. When a gene is turned on, it makes a protein that can affect what the cell looks like and how it behaves. Therefore, to understand what makes a cell in the eye different from a cell in the bones of the hand, we need to know about the genetic switches that control the activity of genes in each cell and tissue.
Here's the important fact: these genetic switches help to assemble us. At conception, we start as a single cell that contains all the DNA needed to build our body. The plan for that entire body unfolds via the instructions contained in this single microscopic cell. To go from this generalized egg cell to a complete human, with trillions of specialized cells organized in just the right way, whole batteries of genes need to be turned on and off at just the right stages of development. Like a concerto composed of individual notes played by many instruments, our bodies are a composition of individual genes turning on and off inside each cell during our development.
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