New protein super-family discovered with critical functions for animal life

Biologists have discovered a new super-family of developmental proteins that are critical for cell growth and differentiation and whose further study is expected to benefit research on cancer and the nerve-cell repair.

The protein super-family, which existed before the emergence of animals about 850 million years ago, is of major importance for understanding how life evolved in primordial times. The discovery will be described in the 14 February 2007 issue of the journal PLoS ONE.

“This super-family is highly divergent, even in animals with an ancient lineage such as the sea anemone. This super-family also evolves rapidly, so its proteins may provide a model system for investigating how rapidly mutating genes contribute to, and are likely necessary for, the diversity and adaptability of animal life,” explains Penn State Assistant Professor Randen Patterson, the senior author of the study. The new protein superfamily is named “DANGER,” an acronym for “Differentiation and Neuronal Growth Evolve Rapidly.”

The discovery was led by Patterson and Damian van Rossum, a postdoctoral scholar at Penn State in University Park, Pennsylvania, and collaborators at Johns Hopkins University in Baltimore, Maryland. “Most DANGER proteins have not been researched, but from what little we do know these proteins, they are critical for cell growth and differentiation,” van Rossum says.

Because so many genomes for diverse organisms have been sequenced and annotated, the discovery of a new and deeply rooted protein family is quite rare. The relationship of the six family members comprising the DANGER super-family escaped detection due to the high rates of mutations between family members, although a few family members had been detected previously and had been shown to control the differentiation of cells into organs in worms, fish, and mice. Deletion of these their DANGER genes led to gross structural changes and prenatal death.

These findings also have clinical relevance, according to the researchers. “Many DANGER proteins are surrounded by transposable elements, which are pieces of DNA around genes that help the genes migrate back and forth throughout the genome,” Patterson says. Because of this feature, DANGER genes can move throughout the genome, which could have positive or negative health consequences. “One member of the gene family resides in the genome at an area responsible for a human disease, the Smith-Magenis syndrome, which results in severe physical and mental retardation,” Patterson explains. “DANGER genes also contain transposable elements that may participate in the genetic disturbances associated with chronic myeleoid leukemia.”

One member of the super-family has been identified as playing a role in the development of the nervous system. “In cell culture and spinal cord neurons, the protein coded for by this gene stimulates lengthening and branching of neurons,” Patterson says. Because many other DANGER proteins also are expressed in neurons, discovering their functions may be a key to deciphering the complexity of neuronal growth and development.

In addition to Patterson and van Rossum, investigators in this study include N. Nikolaidis and D. Chalkia at Penn State and D. N. Watkins, R. K. Barrow, and S. H. Snyder at Johns Hopkins. The research was supported by grants from the National Institutes of Health and the Searle Foundation.

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