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Plants Fix Genes With Copies From Ancestors

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By Rick Weiss

Plants inherit secret stashes of genetic information from their long-dead

ancestors and can use them to correct errors in their own genes -- a

startling capacity for DNA editing and self-repair wholly unanticipated by

modern genetics, researchers said yesterday.

The newly discovered phenomenon, which resembles the caching of early

versions of a computer document for viewing later, allows plants to archive

copies of genes from generations ago, long assumed to be lost forever.

Then, in a move akin to choosing their parents, plants can apparently

retrieve selected bits of code from that archive and use them to overwrite

the genes they have inherited directly. The process could offer survival

advantages to plants suddenly burdened with new mutations or facing

environmental threats for which the older genes were better adapted.

Scientists predicted that by harnessing the still-mysterious mechanism they

would be able to control plant diseases and create novel varieties of

crops. If the mechanism can be invoked in animals -- as some tantalized

scientists venture may be possible -- it could also offer a revolutionary

way to correct the genetic flaws that lead to cancer and other diseases.

" We think this demonstrates that there's this parallel path of inheritance

that we've overlooked for 100 years, and that's pretty cool, " said E.

Pruitt, a professor of botany and plant pathology at Purdue University in

West Lafayette, Ind., who oversaw the studies with co-worker Lolle.

The finding represents a " spectacular discovery, " wrote German molecular

biologists Detlef Weigel and Gerd Jurgens in a commentary accompanying the

research in tomorrow's issue of the journal Nature, released yesterday.

The existence of an unorthodox inheritance system does not overturn the

basic rules of genetics worked out by Austrian monk Gregor Mendel in the

1800s, they noted. But like a newly discovered room in a mansion of

treasures, it opens up a mind-boggling world of possibilities and proves

that genetics is still a young science.

" It adds a level of biological complexity and flexibility we hadn't

appreciated, " said Lolle, who is on a leave from Purdue to serve at the

National Science Foundation, which funded the work.

The Purdue team began to suspect that something strange was afoot while

studying a mutation in the mustard family weed Arabidopsis thaliana, a

popular workhorse of plant genetics.

The mutation was in a gene known as hothead -- one of many related genes,

including fiddlehead, airhead, pothead and deadhead, that when mutated cause

abnormalities in stems and flowers.

Arabidopsis plants typically self-fertilize. So when both copies of a gene

are mutated in a plant, its offspring is bound to be similarly flawed --

in hothead's case, exhibiting the parent's mutant flowers.

Yet in the Pruitt-Lolle lab, a small but steady percentage of hothead

offspring had normal flowers, like their grandparents'. Somehow the mutation

-- a single misspelled " letter " of genetic code in a gene made of 1,782

molecular letters -- was being repaired.

" At first, we assumed there had to be a simple explanation, " Pruitt said.

But a series of tests over more than a year eliminated every easy

explanation, such as known DNA repair mechanisms or windblown pollen from

normal plants.

Instead, molecular studies indicated that the plants harbored molecular

" memories " of versions of their genetic code going back at least four

generations -- versions that the plant can somehow use as templates to

correct the spelling of mutated stretches of DNA.

The team has not found the templates, but evidence suggests they are pieces

of RNA, a molecular cousin of DNA that can be inherited separately from the

chromosomes that carry the primary genetic code in cells.

Pruitt said others have occasionally noted the appearance of " revertant "

plants but ignored them, assuming they were the result of sloppy technique

or other errors. By contrast, Pruitt and Lolle took the observation

seriously, said Elliot Meyerowitz, a pioneering arabidopsis researcher at

California Institute of Technology.

" There are different sorts of scientists. Some like to ignore the

exceptions, and others like to concentrate on them, " Meyerowitz said, adding

that he suspects the novel gene-fixing mechanism is present in a wide

variety of organisms, including animals. He suspects the trick has been

overlooked because it operates only some of the time and because scientists

have been predisposed to write off the evidence as random events.

The discovery, he said, seems on par with a few others that have

significantly modified scientists' understanding of genetics since Mendel.

Studies in corn led to the discovery of an important gene-shuffling

mechanism that has since been found in other plants and animals, including

people. Studies in insects found a new mechanism for gene regulation that

has since been found throughout the biological world. And a mechanism for

turning off genes, first identified in soil-dwelling roundworms and since

found in humans, too, is now one of the hottest topics in medical genetics

because of its potential to shut down disease-causing genes.

" I won't be surprised, " Meyerowitz said, if the new DNA editing mechanism

is present in people, too.

Gerald Fink, a professor of genetics at the Whitehead Institute for

Biomedical Research in Cambridge, Mass., said it would be important to

identify exactly how the mechanism operates and whether it works in all

kinds of genes. But he said he was convinced that " something weird is

definitely going on. " The work serves as a good reminder, he added, that the

central genetic code by itself is only part of the mystery of how

inheritance works.

" This gives the lie to the idea that you know everything once you sequence

the genome. You don't. "

Lolle said the trick is probably a lifesaver for plants, which cannot run

away from radiation, environmental extremes and other insults to their DNA.

It is probably especially important for self-pollinating plants such as

arabidopsis, she said, which are constantly at risk of becoming seriously

mutated as a result of inbreeding.

She described the mechanism as one that allows a plant to reach back in

time for a version of a gene " that's already been road-tested. "

Lolle said she foresees medical benefits as scientists learn to control the

molecular counterpart she suspects is in humans.

" I'm very optimistic, " she said. " Once the scientific community takes hold

of this, it's going to work forward at a very rapid pace. "

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