Genetic Alchemy: Turning Lobsters into Fruit Flies Astrobiology Magazine: http://www.astrobio.net/exclusive/82/genetic-alchemy-turning-lobsters-into-fruit-flies Genetic Alchemy: Turning Lobsters into Fruit Flies 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. Image of Artemia. Credit: Matthew Ronshaugen, UCSD "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. Using laboratory fruit flies and a crustacean known as Artemia, or brine shrimp, the 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 scientists showed how 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. modifications in the Hox gene Ubx which "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 suppresses 100 percent 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." of the limb development in the thoracic region of "All morphological change appears to be based on genetic events of a type somewhat like DOUBLE WINGS: An this one," adds Knoll. "Thus, we are slowly learning the genetic bases for the changes of fruit flies, while its morphological changes seen in the fossil record." ultrabithorax mutant fly has a crustacean counterpart total duplication of the body from Artemia only segment that carries wings. represses 15% would Credit: The Scientist McGinnis and his team now will test to see if an insect version of Ubx will repress limbs have allowed the 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 crustacean-like ancestors of Artemia, 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 with limbs on every mutation of a particular amino acid in the proteins is responsible for the limb repression function. segment, to lose their hind legs and diverge 400 million years ago into the six-legged insects. Credit: Matthew Ronshaugen, UCSD "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." What Next? Brine shrimp are multi-limbed. Let us review some Biology 11: The Phylum Arthropoda have several subphyla and classes. Some arthropod classes have multi-segmented / multi-limbed adults, often with two pairs of legs per segment. Examples include Centipedes and Millipedes. Crustacea are also Arthopods; but as adults they have two or three body sections. Many Crustacea (like brine-shrimp) are still multi-limbed as adults. The Arthropod Class Insecta also have larvae with many segments (like everything mentioned so far). However, insect adults have bodies divided into three parts: head, thorax and abdomen with three pairs of legs and usually one (maybe two) pairs of wings attached ONLY to the thorax. Check out the diagrams in the article. Do brine-shrimp have insect-like ancestors, or do insects have brine-shrimp-like ancestors? Explain - What evidence do we have? ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ Hox” is actually a nickname for ________________________________________________________________________ Describe what “Hox”genes do: ________________________________________________________________________ _________________________________________________________________________________________________ “Ubx” is actually a nickname for _______________________________________________________________________ Describe what happens when “Ubx”gene expression is removed in insects: ____________________________________ _________________________________________________________________________________________________ Is “Ubx”gene expression turned on or off in fly thoraxes? Explain ___________________________________________ _________________________________________________________________________________________________ Transgenic flies were constructed. What happens when the brine shrimp version of the “Ubx”gene expression is inappropriately expressed in fly thoraxes? __________________________________________________________________________________________________ __________________________________________________________________________________________________ Remember that flies have segmented larvae. Why would an ultrabithorax mutant fly (shown in the article) have a total duplication of the body segment that carries wings? __________________________________________________________________________ __________________________________________________________________________ This insect fossil found in Kentucky (1980) was an insect wing from the Pennsylvanian rocks of the Eastern Kentucky Coal Field. It came from an animal that had a wing span of about 4 inches, looked somewhat like a dragonfly, and could not fold up its wings. This fossil has 3 sets of wings (the first set is smaller). Speculate what an even earlier ancestor may have looked like look like. _____________________________________________________________________________ ______________________________________________________________________________ It would appear that timing of Ubx expression during development is important. What are the next series of experiments the scientists want to attempt? _____________________________________________________________ __________________________________________________________________________________________________ This is a great article. But you cannot always believe everything you read! The well known homeotic genes in plants (MADS-box genes) are NOT homologous to Hox genes in animals. Plants and animals do NOT share the same homeotic genes, and this suggests that homeotic genes arose INDEPENDENTLY in the early evolution of animals and plants. When did Hox genes first appear in animal evolution? __________________________________________________________________________________________________ When did segmentation first appear in animal evolution? __________________________________________________________________________________________________ Why would the separate evolution of Hox-like genes in plants make sense? Explain (hint – vascular tissue in leaves, stems & roots?) __________________________________________________________________________________________________ __________________________________________________________________________________________________ Should humans be considered a segmented animal? Explain. _______________________________________________ __________________________________________________________________________________________________ __________________________________________________________________________________________________