Boston, MA -- February 3, 2000 -- The evolutionary transition from life in the sea to life on land may have been nudged by a genetic expansion, according to an article appearing in the February Development. HMS researchers Susan Dymecki and her colleagues suggest that a gene previously expressed in the developing brain may have come to be expressed also in the tips of developing limbs, helping to bring about the development of toes and fingers in the first vertebrates.

"So you get expansion of gene expression--not expression of a new gene--just expansion to a new area," says Dymecki, HMS assistant professor of genetics. She and colleagues Scott Baur and Jia J. Mai have recently identified the structure of the gene and also the genetic switch that may have brought about this expansion.

Until recently, the gene, which codes for a receptor found in the brains and skeletons of all vertebrates living today, was thought to be controlled by a single switch, or promoter. If that were true, a defect in the promoter should affect expression in the brain as well as the skeleton. But the researchers found that while mutant mice carrying such a defect almost totally lacked fingers and toes, their brains appeared, for the most part, normal. On closer inspection, the researchers found that there was not one but two promoters, one controlling gene expression in the brain, the other, which carried the mutation, in the limbs. The defective promoter was farthest away from the gene. "This is the first time anyone has seen this distal promoter," says Dymecki.

She and Baur, who is a graduate student, believe that this more distant promoter evolved more recently, perhaps as a result of a duplication of the one lying closer to the gene. Once formed, the new promoter may have accumulated mutations that enabled it to interact with transcription factors found in developing limb cells. As a consequence, the receptor previously expressed in the brain would have come to be expres
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Contact: Peta Gillyatt
gillyatt@hms.harvard.edu
617-432-0443
Harvard Medical School
2-Feb-2000