UC Berkeley researchers explain key mechanism of inheritance that defies Mendel’s first law of genetics

February 27, 2009

Researchers at the University of California, Berkeley, have discovered a key mechanism responsible for a curious type of genetic inheritance that has been one of the great, unsolved mysteries in biology. The new findings, to be published today (Friday, Feb. 27) in Science, help explain the phenomenon of paramutation, in which certain alleles are heritably altered while their DNA sequences remain unchanged.

Paramutation violates the first law of genetics: that alleles are always inherited unchanged from the previous generation. The phenomenon was first described in 1956 for one of the factors responsible for corn-seed coloration. Since then, it has been observed in several plant species, and in 2006 an international group of researchers described an example of paramutation in mice, reinvigorating the idea that the phenomenon might represent a more fundamental aspect of biology.

The Berkeley researchers, led by Jay Hollick, associate adjunct professor of plant biology, returned to the corn plant to examine how paramutation works. They discovered that a plant-specific RNA polymerase Pol IV is responsible for the multi-generational memory of paramutation as well as normal plant development. This unusual RNA polymerase is responsible for the production of small RNA molecules from repetitive non-coding DNA.
The researchers noted that removing the action of Pol IV in Arabidopsis, another model plant species, has no effect. Because the corn genome is nearly 200 times that of Arabidopsis due to the expansion of non-gene sequences, the researchers deduced that in the corn genome, Pol IV acts upon one or more of the ubiquitous non-coding units of DNA to ensure proper development.

“Our work indicates that what many biologists have considered ‘junk’ or non-coding DNA has functional significance for defining the factors that are passed from generation to generation,” said Hollick.

Hollick said that if scientists can identify how non-coding DNA sequences contribute to the development of heritable characteristics, this understanding could help breeders improve techniques for achieving desired outcomes with a wide variety of organisms. “This understanding may have profound implications for both the future of agriculture and human health,” he said.

The work is funded by the US Department of Agriculture and the National Science Foundation. Other co-authors contributing to this work include lead author Karl Erhard, Jennifer Stonaker, Susan Parkinson, Jana Lim, and Christopher Hale, all of UC Berkeley’s Department of Plant and Microbial Biology.