In an advance online publication February 6 by Nature of a paper scheduled to appear in Nature, the scientists show how mutations in regulatory genes that guide the embryonic development of crustaceans and fruit flies allowed aquatic crustacean-like arthropods, with limbs on every segment of their bodies, to evolve 400 million years ago into a radically different body plan: the terrestrial six-legged insects.

The achievement is a landmark in evolutionary biology, not only because it shows how new animal body plans could arise from a simple genetic mutation, but because it effectively answers a major criticism creationists had long leveled against evolution-the absence of a genetic mechanism that could permit animals to introduce radical new body designs.

"The problem for a long time has been over this issue of macroevolution," says William McGinnis, a professor in UCSD's Division of Biology who headed the study. "How can evolution possibly introduce big changes into an animal's body shape and still generate a living animal? Creationists have argued that any big jump would result in a dead animal that wouldn't be able to perpetuate itself. And until now, no one's been to demonstrate how you could do that at the genetic level with specific instructions in the genome."

The UCSD team, which included Matthew Ronshaugen and Nadine McGinnis, showed in its experiments that this could be accomplished with relatively simple mutations in a class of regulatory genes, known as Hox, that act as master switches by turning on and off other genes during embryonic development. Using laboratory fruit flies and a crustacean known as Artemia, or brine shrimp, the scientists showed how modifications in the Hox gene Ubx-which suppresses 100 percent of the limb development in the thoracic region of fruit flies, but only 15 percent in Artemia-would have allowed the crustacean-like ancestors of Artemia, with limbs on every segment, to lose their hind legs and diverge 400 million years ago into the six-legged insects.

"This kind of gene is one that turns on and off lots of other genes in order to make complex structures," says Ronshaugen, a graduate student working in William McGinnis' laboratory and the first author of the paper. "What we've done is to show that this change alters the way it turns on and off other genes. That's due to the change in the way the protein produced by this gene functions."

"The change in the mutated protein allows it to turn off other genes," says William McGinnis, who discovered with two other scientists in 1983 that the same Hox genes in fruit flies that control the placement of the head, thorax and abdomen during development are a generalized feature of all animals, including humans. "Before the evolution of insects, the Ubx protein didn't turn off genes required for leg formation. And during the early evolution of insects, this gene and the protein it encoded changed so that they now turned off those genes required to make legs, essentially removing those legs from what would be the abdomen in insects."

The UCSD team's demonstration of how a mutation in the Ubx gene and changes in the corresponding Ubx protein can lead to such a major change in body design undercuts a primary argument creationists have used against the theory of evolution in debates and biology textbooks. Their specific objection to the idea of macroevolutionary change in animals is summed up in a disclaimer that the Oklahoma State Textbook Committee voted in November, 1999 to include in that state's biology textbooks: "The word evolution may refer to many types of change. Evolution describes changes that occur within a species. (White moths, for example, may evolve into gray moths). This process is microevolution, which can be observed and described as fact. Evolution may also refer to the change of one living thing into another, such as reptiles and birds. This process, called macroevolution, has never been observed and should be considered a theory."

"The creationists' argument rests in part on the fact that animals have two sets of chromosomes and that in order to get big changes, you'd need to mutate the same genes in both sets of chromosomes," explains McGinnis. "It's incredibly unlikely that you would get mutations in the same gene in two chromosomes in a single organism. But in our particular case, the kind of mutation that's in this gene is a so-called dominant mutation, so you only need to mutate one of the chromosomes to get a big change in body plan."

The discovery of this general mechanism for producing major leaps in evolutionary change has other implications for scientists. It may provide biologists with insights into the roles of other regulatory genes involved in more evolutionarily recent changes in body designs. In addition, the discovery in the UCSD study, which was financed by the National Institute of Child Health and Human Development, of how this particular Hox gene regulates limb development also may have an application in improving the understanding human disease and genetic deformities.

"If you compare this gene to many other related genes, you can see that they share certain regions in their sequences, which suggests that their function might be regulated like this gene," says Ronshaugen. "This may establish how, not only this gene, but relatives of this gene in many, many different organisms actually work. A lot of these genes are involved in the development of cancers and many different genetic abnormalities, such as syndactyly and polydactyly, and they may explain how some of these conditions came to be."

Note: If no author is given, the source is cited instead.

• Evolutionary Biology
• Life Sciences
• Genetics

• Evolution
• Charles Darwin
• Origin of Life

• Speciation
• Morphogenesis
• Mutation
• Genetic drift
• Arthropod
• Natural selection