Contrary to inheritance laws the scientific world has accepted for more than 100 years, some plants revert to
normal traits carried by their grandparents, bypassing genetic abnormalities carried by both parents.

These mutant parent plants apparently have hidden templates containing genetic information from the preceding generation that can be transferred to their offspring, even though the traits aren't evident in the parents, according to Purdue University researchers. This discovery flies in the face of the scientific laws of inheritance first
described by Gregor Mendel in the mid-1800s and still taught in classrooms around the world today.

"This means that inheritance can happen more flexibly than we thought in the past," said Robert Pruitt, a Purdue Department of Botany and Plant Pathology molecular geneticist. "While Mendel's laws that we learned in high school still are fundamentally correct, they're not absolute.

"If the inheritance mechanism we found in the research plant Arabidopsis exists in animals, too, it's possible that it will be an avenue for gene therapy to treat or cure diseases in both plants and animals."

The study is published in the March 24 issue of the journal Nature.

Pruitt and collaborator Susan Lolle found that Arabidopsis in which each parent plant had two copies of a mutant gene could produce progeny that didn't show the parents' deformity, but rather were normal like the grandparents. Under Mendelian laws, the offspring should have shown the same mutation.

The first clue that the classic inheritance rules didn't always apply was the discovery of normal flowers on some offspring of mutant plants. In the deformed parents, the flowers were fused into tight balls. But in the grandparents and 10 percent of the grandchildren, the buds become 1-millimeter-long, bright white flowers that fully opened and radiated out from the center of a cluster.

"If you take this mutant Arabidopsis, which has two copies of the altered gene, let it seed and then plant the seeds, 90 percent of the offspring will look like the parent, but 10 percent will look like the normal grandparents," Pruitt said. "Our genetic training tells us that's just not possible. This challenges everything we believe.

"We've done a lot of experiments, described in this paper, that show  none of the simple explanations account for this skipping ofgenerations by an inherited trait."

The scientists kept the plants in isolation so they couldn't accidentally crossbreed with plants that didn't have the mutated gene, called hothead, that causes organ fusion like that seen in the flowers. The researchers used molecular markers - bits of DNA that help identify and locate genes in organisms - to determine whether a plant carried normal or mutant copies of the genes.

"It seems that these hothead-containing plants keep a cryptic copy of everything that was in the previous generation, even though it doesn't show up in the DNA, it's not in the chromosome," Pruitt said. "Some other type of gene sequence information that we don't really understand yet is modifying the inherited traits."

Although the hothead gene tipped the researchers off to this unconventional inheritance cycle, Pruitt believes that this particular DNA sequence is just a trigger for the phenomenon. He suspects that a number of other genes and the proteins they produce are involved in activating this process.

"We need to understand more about the molecular mechanics of how this process works," Pruitt said. "Then we will know exactly what role this gene plays."

Pruitt's team already knows that animals don't have hothead genes, either normal or mutated, so the scientists must investigate which genes might affect this novel inheritance in both plants and animals.

"There are probably a lot of other triggers yet to be discovered, and this mechanism for inheritance may require a different trigger to make it work in animals," he said.

Once scientists understand more about the mechanism, they then may be able to manipulate it to modify genes already in plants and animals in order to correct mutations that cause diseases and abnormal growth.

Though further research is required to learn how this form of inheritance happens and how it can help improve plants or animals through gene therapy, Pruitt said the discovery has opened an important new line of thinking.

The other researchers involved with this study were Jennifer Victor, a former Purdue graduate student now at Butler University; and Jessica Young, a botany and plant pathology laboratory technician. Lolle, a Purdue research scientist, is currently at the National Science Foundation.

The National Science Foundation provided funding for this research.

Related Web sites:

Purdue Department of Botany and Plant Pathology: http://www.btny.purdue.edu/
Nature: http://www.nature.com/nature/index.html
National Science Foundation: http://www.nsf.gov/

ABSTRACT

Genome-wide non-Mendelian inheritance of extra-genomic information in Arabidopsis
Susan J. Lolle*, Jennifer L. Victor, Jessica M. Young & Robert E. Pruitt* (Department of Botany and Plant Pathology, Purdue University, 915 W. State Street, West Lafayette, Indiana 47907-2054, USA) - * These authors contributed equally to the work

A fundamental tenet of classical Mendelian genetics is that allelic information is stably inherited from one generation to the next, resulting in predictable segregation patterns of differing alleles1. Although several exceptions to this principle are known, all represent specialized cases that are mechanistically restricted to either a limited set of specific genes (for example mating type conversion in yeast2) or specific types of alleles (for example alleles containing transposons3 or repeated sequences4). Here we show that Arabidopsis plants homozygous for recessive mutant alleles of the organ fusion gene HOTHEAD5 (HTH) can inherit allele-specific DNA sequence information that was not present in the chromosomal genome of their parents but was present in previous generations. This previously undescribed process is shown to occur at all DNA sequence polymorphisms examined and therefore seems to be a general mechanism for extragenomic inheritance of DNA sequence information. We postulate that these genetic restoration events are the result of a template-directed process that makes use of an ancestral RNA-sequence cache.