Probably the last place you should look for Greg Wray is in his office. You might find him sitting in another professor’s guest chair, talking about sea urchins, baboons, or maybe lichen. He could be teaching a class about dinosaurs. Or perhaps he’s somewhere around the genome-sequencing facility he directs, a suite of high-powered equipment in the Biological Sciences Building that can read through the entire genetic code of an organism in less than a day. His assistant talks to him mostly through cell-phone texts.
What looks like distracted, omnivorous behavior is in fact a single-minded pursuit. Wray Ph.D. ’87, a fifty-one-year-old professor of biology at Duke, is after a big question surrounding the origin of species, one that has led him to collaborate with dozens of scientists while studying organisms as diverse as great white sharks and fire ants.
“This is the greatest time to be a biologist,” Wray begins during a rare moment in his own office on the fourth floor of the French Family Science Center. Like a lot of professors’ warrens, it’s lined floor-to-ceiling with books. But there is also a large collection of toy dinosaurs and two skulls, one a heavy-browed pre-human, the other a small, crocodile-like caiman. At the level of biology Wray cares most about, all of these creatures are basically the same. “When you drill down to the molecules and the genetics, it’s a lot of the same stuff,” he says. “We use urchins on one hand and primates on the other because they allow us to see different aspects of the same problem.”
The “problem” is how a relatively small set of genes—fewer than 25,000 in both humans and chimpanzees—can produce such complex and dramatically different organisms. For that matter, why do humans, with our spectacular brains and versatile digestive abilities, have only a handful more genes than a brainless, one-millimeterlong worm that eats nothing but bacteria?
The answer that Wray and a growing number of evolutionary biologists are pursuing is that our 25,000 genes are merely sheet music: It’s how that music is played that makes us different. Wray was among the first to argue, and then to document, that evolution acts on those “players”—the sections of DNA that regulate how genes are expressed—making them key drivers of the diversity of life.
All he had to do was find them.
In 1975, when Greg Wray was still in high school, Stanford biologists Mary Claire King and Allan Wilson compared a sampling of proteins and short portions of DNA from humans and chimpanzees—the best they could do with contemporary techniques—and published the remarkable finding that humans and chimps appeared to be 99 percent the same on the genetic level. This immediately raised an enormous question of how we could be so alike in our nuclei, and yet so different in behavior, diet, intellect, physiology, and body hair. King and Wilson proposed that the expression of genes, their on and off patterns, would account for much of the difference. But the tools just weren’t ready to address that question.
At the beginning of this century, computerized and robotic lab technology enabled the reading of complete genomes, first for the model species like yeast, nematodes, and fruit flies, and then for pathogens, crops, humans, and chimpanzees. A curious pattern emerged: Huge sections of the DNA didn’t describe proteins, the structural elements and chemical actors that sustain life. In fact, among the 3 billion letters of the human genome, only 2 percent of the DNA was found to code for proteins. Was the rest of the genome simply rough drafts and broken bits left over from the chaos of mutation and natural selection? Surely there had to be more to the system, but it wasn’t easy to see.
Yet a big part of the answer to this socalled “junk DNA” was already somewhat known. Every cell that has a nucleus carries a complete copy of the genome—all of the DNA required to build and operate an organism from fertilized egg to senescence. But all of those genes can’t be active all of the time in every cell; if they were, you’d have fingernails on the palm of your hand and hair on your gums. So it was clear that genes are carefully coordinated to work only when and where they are needed— and to stay quiet and out of the way where they aren’t—a process called expression. Gene expression makes an embryo into a fetus and then an adolescent using just one set of genes.
What wasn’t quite so obvious—until it became possible to look at millions of letters of DNA pretty much all at once—was that gene expression also helped create the mosaic of species around us. Wray was one of the first biologists to argue that natural selection could shape not just the genes themselves, but also the regulatory regions that orchestrate turning genes on and off. He reasoned that evolutionary changes in these “switches” could allow similar genomes to take on a radically different appearance from one individual to the next or one species to the next.
With a million or so of these switches controlling the expression of genes in interconnected circuits and feedback loops, biology has an exquisite tool for fine-tuning the organism, Wray says. An invading army of bacteria swarming through a cut in the skin triggers a chemical signal that causes millions of the host’s cells to swing into action, cranking out legions of bugfighting white blood cells and raising the body’s temperature. When the infection is defeated, the signal stops, the temperature drops, and the white blood cells dissipate. “The regulatory region of the DNA,” Wray says, “is like a scaffold on which different proteins come and sit down. Different combinations of these proteins turn on or off specific genes. They act as switches that regulate under which conditions a gene will be on or not.”
To see how natural selection might bring such a system to pass, imagine a tiger’s stripes, which are produced by gene expression turning on black pigment in some hair follicles and orange or white in others. If this system of expression didn’t work, the tiger would be without her camouflage and would probably capture fewer prey as a result. That in turn would mean fewer, weaker offspring, whereupon natural selection eventually would take the stripeless tigers out of the gene pool. But this is what biologists call a “just-so” story—a narrative that seems plausible but lacks real data. Wray’s colleagues demanded proof. “The challenge was getting the right kind of data together to convince the community,” he says.