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How were body plans able to undergo large-scale changes during the course of evolution? For instance, how did something that looked like a centipede evolve into something as different as a fruit fly? This is a question that has long concerned biologists that study evolutionary history. Genetic mutations that would dramatically alter body structures could potentially kill an organism before it even had a chance to live.

Biologists at the University of California, San Diego, now have genetic evidence that explains how such drastic alterations to body plans were able to occur during the early evolution of animals.

In a paper published in the Feb. 21st issue of Nature, Matthew Ronshaugen, Nadine McGinnis, and William McGinnis describe how a simple genetic mutation caused aquatic arthropods, with limbs on every segment of their bodies, to evolve 400 million years ago into the radically different body plans of terrestrial six-legged insects.

The UCSD team says a mutation occurred in a class of regulatory genes known as homeotic, or “Hox” genes. Hox genes act as master switches, turning on and off other genes during embryonic development. Hox genes determine the fate of each cell in the embryo, ensuring that organs and other body parts form properly in the developing animal.

A particular Hox gene called Ultrabithorax, or “Ubx,” regulates limb formation. In insects, Ubx suppresses development of wings and legs in the abdomen, ensuring that only the thorax develops these structures. If the Ubx gene is removed from modern insects such as fruit flies, they develop legs sprouting from every abdominal segment.

The insect Ubx gene can also suppress 100 percent of leg development when it is inappropriately activated in the thorax. The UCSD team found that a Ubx protein derived from a multi-limbed crustacean (Artemia, or brine shrimp) could only suppress 15 percent of the limb development when activated in the thoracic region of fruit flies. But when the scientists made a few mutations in the crustacean version of the Ubx protein to make it more similar to insect Ubx, the protein was able to suppress all limb development.

“This kind of gene is one that turns on and off lots of other genes in order to make complex structures,” says Ronshaugen. “What we’ve done is to show that this change alters the way it turns on and off other genes.”

The difference in Ubx protein limb suppression between fruit flies and Artemia reflects the development of the gene over time. The ancestor of these two organisms had limbs on every body segment. Over the course of evolution, the Ubx protein developed to turn off the genes needed for leg formation. The fossil record shows examples of various arthropod body plans that evolved because of the development of this gene – for example, early insects tended to have more sets of wings and legs than are seen in modern insects.

“What is new in this study is that a change in a regulatory gene – in this case the Ubx gene – can have dramatic morphological consequences,” says Andrew Knoll, a paleobiologist with Harvard University who was not involved in the study. “We’ve long known that mutations in regulatory networks drive morphological evolution, but most discussion focused on timing of gene expression. Here, it is a structural change that alters the regulatory pattern.”

Hox genes are found in all animals, including humans. Hox genes seem to have developed fairly early in the history of life on Earth, and may therefore provide vital clues about the course of evolution.

“Land plants contain Hox homologs, so it seems that the ancestral Hox-like gene existed in the last common ancestor of plants and animals, which was a unicellular organism that lived at least 1200 million years ago,” says Knoll. “The oldest fossils whose morphology implies a set of Hox genes controlling anterior-posterior patterning are 555 million year old animal traces from northern Russia.”

Scientists had already suspected that Hox mutations could cause dramatic changes in body plans. One argument against this possibility was that, since each chromosome in a pair has its own Hox genes, you would need to get the same Hox mutation on both chromosomes in order to see changes in body structure.

“It’s incredibly unlikely that you would get mutations in the same gene in two chromosomes in a single organism,” says McGinnis. “But in our particular case, the kind of mutations that occur in this gene are so-called dominant mutations, so you only need to mutate one of the chromosomes to get a big change in body plan.”

“All morphological change appears to be based on genetic events of a type somewhat like this one,” adds Knoll. “Thus, we are slowly learning the genetic bases for the changes of morphological changes seen in the fossil record.”

What’s Next

McGinnis and his team now will test to see if an insect version of Ubx will repress limbs when expressed during embryonic development in crustaceans. They are conducting this test in collaboration with Bill Browne and Nipam Patel at the University of Chicago, on the amphipod crustacean Parhyale hawaiensis

They also plan to clone Ubx and AbdA genes from other crustaceans, as well as other types of multi-limbed arthropods like millipedes and centipedes. They will test to see if these genes also can repress limbs in fruit fly embryos. This test may help determine whether a mutation of a particular amino acid in the proteins is responsible for the limb repression function.