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Appetite gene suspected in pigs
By Bijal P. Trivedi

Geneticists have found that different forms of a particular gene can cause a pig to make a real pig of itself.

"Some pigs have a form of the gene that makes them eat more and they grow faster and get fatter," says Max Rothschild, a geneticist at Iowa State University. "Others have a different form of the gene that creates pigs that are leaner, eat less, and grow slowly." Rothschild and his colleagues report their research on the melanocortin-4 receptor gene (MC4R), which occurs in all mammals, in a recent issue of Mammalian Genome.

Rothschild's group became interested in the gene after Millennium Pharmaceuticals Inc. found that mice lacking MCR4 "eat like crazy" and become really fat, says Rothschild. This finding spurred Rothschild, whose research focuses on genes that influence livestock, to look for different forms of the gene in pigs.

They determined the version of the MC4R gene for 1,800 pigs and then measured the backfat—a standard measure of pig fatness—food intake and growth rate for each animal. Examining the protein encoded by the MCR4 gene, the team found that changing a single amino acid subunit caused a significant difference in fatness. Pigs having aspartic acid as the 298th amino acid in the protein had nine percent less backfat and grew significantly more slowly than pigs with asparagine in that position. How a difference in a single amino acid causes such a dramatic effect in this protein remains a mystery, but Rothschild has a suggestion. The protein functions on the surface of brain cells, affecting the pig's appetite. He suspects the amino acid substitution changes the protein's ability to accept signals coming into cells, effectively turning the hunger dial down a few notches.

Rothschild's work is part of a larger project to find commercially important genes in the pig. Genes affecting litter size, food intake and meat quality could have tremendous commercial value. Iowa is the number one pork producer in the country with about 25 million pigs per year, and pork accounts for 40 percent of global red meat consumption, says Rothschild.

Farmers have manipulated animal genetics for thousands of years. The traditional approach involves selecting traits, such as meat quality or litter size, and then breeding animals with the desired characteristics. The selective breeding should produce animals with desirable genes. But it can take up to a decade of such breeding before a farmer can be sure a trait is consistently passed to the next generation.

Once a gene has been discovered, however, genetic testing can offer a shortcut, says Rothschild. The tests can give researchers direct information about which genes an animal carries. Rothschild, the U.S. Pig Genome Coordinator, has developed a genetic test that predicts which pigs will have large litters. Rothschild hopes new gene discoveries will allow selection of a wide variety of traits in pigs.

For now, he has to settle for lots of piglets that really pig out.

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Kim, S.K., Larsen, N., Short, T., Plastow, G., & Rothschild, M.F. A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits. Mamm Genome 11, 131-135 (February 2000).

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