Are genes our destiny?

September 15, 2011 LA JOLLA, CA—A "hidden" code linked to the DNA of plants allows them to develop and pass down new biological traits far more rapidly than previously thought, according to the findings of a groundbreaking study by researchers at the Salk Institute for Biological Studies.

The study, published today in the journal Science, provides the first evidence that an organism's "epigenetic" code - an extra layer of biochemical instructions in DNA - can evolve more quickly than the genetic code and can strongly influence biological traits.

While the study was limited to a single plant species called Arabidopsis thaliana, the equivalent of the laboratory rat of the plant world, the findings hint that the traits of other organisms, including humans, might also be dramatically influenced by biological mechanisms that scientists are just beginning to understand.

"Our study shows that it's not all in the genes," said Joseph Ecker, a professor in Salk's Plant Molecular and Cellular Biology Laboratory, who led the research team. "We found that these plants have an epigenetic code that's more flexible and influential than we imagined. There is clearly a component of heritability that we don't fully understand. It's possible that we humans have a similarly active epigenetic mechanism that controls our biological characteristics and gets passed down to our children. "

With the advent of techniques for rapidly mapping the DNA of organisms, scientists have found that the genes stored in the four-letter DNA code don't always determine how an organism develops and responds to its environment. The more biologists map the genomes of various organisms (their entire genetic code), the more they are discovering discrepancies between what the genetic code dictates and how organisms actually look and function.

In fact, many of the major discoveries that led to these conclusions were based upon studies in plants. There are traits such as flower shape and fruit pigmentation in some plants that are under the control of this epigenetic code. Such traits, which defy the predictions of classical Mendelian genetics, are also found in mammals. In some strains of mice, for instance, a tendency for obesity can pass from generation to generation, but no difference between the genetic code of fat mice and thin mice explains this weight difference.

Scientists have even found that identical human twins exhibit different biological traits, despite their matching DNA sequences. They have theorized that such unexplained disparities could be the work of epigenetic variation.

"Since none of these patterns of variation and inheritance match what the genetic sequence says should happen, there is a clearly a component of the 'genetic' heritability that is missing," Ecker said.

Ecker and other scientists have traced these mysterious patterns to chemical markers that serve as a layer of genetic control on top of the DNA sequence. Just as genetic mutations can arise spontaneously and be inherited by subsequent generations, epigenetic mutations can emerge in individuals and spread into the broader population.

Although scientists have identified a number of epigenetic traits, very little was known about how often they arose spontaneously, how quickly they could spread through a population and how significant an influence they could have on biological development and function.

"Perception of the extent of epigenetic variation in plants from generation to generation varies widely within our scientific community," said Robert Schmitz, a post-doctoral research in Eckers' laboratory and the lead author on the paper. "We actually did the experiment, and found that overall there is very little change between each generation, but spontaneous epimutations do exist in populations and arise at a rate much higher than the DNA mutation rate, and at times they had a powerful influence over how certain genes were expressed."

In their study, the Salk researchers and collaborators at Scripps Research Institute mapped the epigenome of a population of Arabidopsis plants then observed how this biochemical landscape had changed after 30 generations. This mapping consisted of recording the state of all locations on the DNA molecule that could undergo a chemical modification known as methylation, a key epigenetic change that can alter how certain underlying genes are expressed. They then watched how methylation states of these sites evolved over the generations.

 About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

For more information:

Science 

September 15 [Epub ahead of print]

Authors: Schmitz, R.J., Schultz, M.D., Lewsey, M.G., O'Malley, R.C., Urich, M.A., Libiger, O., Schork, N.J., Ecker, J.R.

Instability Is a Source of Novel Methylation Variants