Published by the MIT News Office at the Massachusetts Institute of Technology, Cambridge, Mass.
Published by the MIT News Office at the Massachusetts Institute of
Technology, Cambridge, Mass.
IMPROVED PLANTS Broccoli Enzyme May Aid Genetic Understanding By Elizabeth A. Thomson News Office Broccoli and a small weed are helping MIT biologists unlock the secrets of how genes are pieced together in plant cells. The work could eventually pave the way for genetically engineered plants that scientists have been unable to develop so far; plants with better nutritional value, tolerance to drought, resistance to certain pests and diseases, and other useful and important traits. Recently Professor Ethan R. Signer of biology and colleagues took a step forward in the research by isolating enzymes from broccoli that could be critical to the process of introducing an engineered gene to a plant. In related work, the researchers are continuing their studies of Arabidopsis thaliana, a small weed that genetic engineers have coined "the fruit fly of the plant world" for its many uses in genetic studies. The enzyme and Arabidopsis studies are part of a comprehensive effort led by Professor Signer to understand genetic recombination in plants. In the process, the researchers hope to overcome a problem currently thwarting genetic engineers in their attempts to give plants a variety of useful traits. In general, biologists would like to make genetically engineered plants by replacing a specific gene in a plant's genetic repertoire with a variant of that gene that determines some valuable trait. Theoretically the plant should then show the engineered trait-say, improved nutritional value-and pass it on to future generations. But it doesn't always work that way. In the vast majority of cases the altered gene adds to a plant's total number of genes, rather than replacing the original gene. And addition rather than replacement causes serious problems. For one, scientists can't control where the altered gene will end up in the genome. "For some genes, the exact position on the right chromosome probably matters," said Professor Signer. "Things might go wrong if that gene is in the wrong location." Second, and perhaps most importantly, the altered gene is often recessive to-or masked by-the original gene. So the plant won't show the trait that geneticists worked so hard to add. It turns out that many important traits like crop yield and drought tolerance are very likely determined by recessive genes. "Some genetic-engineering methods to confer pest or herbicide resistance involve dominant genes, so geneticists are trying them now," said Professor Signer, "but other traits almost certainly involve recessive genes, and geneticists can't do anything about those now using genetic engineering." For all these reasons, if biologists could get an engineered gene to consistently replace the original gene rather than add to the total number of genes, a wide variety of plants with important improvements would be closer to reality. Enter the MIT work. "We're running a whole program directed at understanding genetic recombination, a large part of which has to do with gene replacement," Professor Signer said. For example, in one research effort Professor Signer and Alain Tissier, a visiting scientist, recently isolated enzymes from broccoli that they believe could be critical to solving the addition/replacement problem. (Mr. Tissier is continuing work by graduate student Joseph Kieber and postdoctoral associate Mary Lopez, who have since left MIT.) Strand-exchange enzymes, or recombinases, are largely responsible for cutting and pasting a gene into a chromosome. As a result, the scientists hope that by tinkering with the genes that code for these recombinases, and with other related genes, they can get the enzymes to direct more replacement than addition. Professor Signer emphasizes that "the same type of enzymes have been found in many other organisms," but these recombinases are the first to be isolated from broad-leaved plants. In other work, Signer and colleagues are studying genetic events in Arabidopsis thaliana, a small weed valued in genetic studies for its small size, rapid growth rate and relatively small amount of genetic material. Part of the research involves inserting a piece of foreign DNA into a number of plants to watch how the DNA recombines over several generations and under a variety of conditions. Graduate students Farhah Assaad and Kerry Tucker have been working on these studies. Professor Signer points out that plant biology is about 10-15 years behind mammalian biology. As a result, the group is trying some of the same approaches on plants that work in the mouse to get genes that replace. At the same time, they are developing new approaches specifically for plants. "In mice, if you look carefully at what's going on," Professor Signer explained, "a gene from the outside will add most of the time, but maybe 1 in 100 to 1 in 1,000 times that gene will actually replace by natural processes." Using technical tricks scientists can throw away the cells in which genes added, so they only end up with cells in which genes have replaced. Natural replacement also happens in plants, so "we'd like to develop similar kinds of selective tricks to get the needle out of the haystack," Professor Signer said. "If we can make these tricks work in a model system, then other people will be able to use them in practical applications." Postdoctoral associates Ramesh Sonti, Maurizio Chiurezzi and Ranjan Perera, and senior Cole Reinwand are working on replacement. They are continuing work by postdoctoral associates Animesh Ray and Abdul Chaudhury, who have since left MIT, and Lama Rimawi, SB `91. All of these studies could one day lead to a variety of important new plants. In the meantime, Professor Signer points to the value of understanding just that much more about how genes interact in the cell. "For me," he said, "the process is interesting for itself, besides being useful in a practical sense."