STARTLING !PLANT FIXES ITS FLAWED GENE !

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Startling Scientists, Plant Fixes Its Flawed Gene

In a startling Discovery, geneticists at Purdue University
say they have found plants that possess a corrected version of a defective gene
inherited from both their parents, as if some handy backup copy with the right
version had been made in the grandparents’ generation or earlier.

The finding implies that some organisms may contain a
cryptic backup copy of their genome that bypasses the usual mechanisms of
heredity. If confirmed, it would represent an unprecedented exception to the
laws of inheritance discovered by Gregor Mendel in the 19th century. Equally
surprising, the cryptic genome appears not to be made of DNA, the standard
hereditary material.

The discovery also raises interesting biological questions
– including whether it gets in the way of evolution, which depends on mutations
changing an organism rather than being put right by a backup system.

“It looks like a marvelous discovery,” said Dr. Elliott
Meyerowitz, a plant geneticist at the California Institute of Technology. Dr.
David Haig, an evolutionary biologist at Harvard, described the finding as “a
really strange and unexpected result,” which would be important if the
observation holds up and applies widely in nature.

The result, reported online yesterday in the journal Nature
by Dr. Robert E. Pruitt, Dr. Susan J. Lolle and colleagues at Purdue, has been
found in a single species, the mustardlike plant called arabidopsis that is the
standard laboratory organism of plant geneticists. But there are hints that the
same mechanism may occur in people, according to a commentary by Dr. Detlef
Weigel of the Max-Planck Institute for Developmental Biology in Tübingen,
Germany. Dr. Weigel describes the Purdue work as “a spectacular discovery.”

The finding grew out of a research project started three
years ago in which Dr. Pruitt and Dr. Lolle were trying to understand the genes
that control the plant’s outer skin, or cuticle. As part of the project, they
were studying plants with a mutated gene that made the plant’s petals and other
floral organs clump together. Because each of the plant’s two copies of the gene
were in mutated form, they had virtually no chance of having normal
offspring.

But up to 10 percent of the plants’ offspring kept
reverting to normal. Various rare events can make this happen, but none involve
altering the actual sequence of DNA units in the gene. Yet when the researchers
analyzed the mutated gene, known as hothead, they found it had changed, with the
mutated DNA units being changed back to normal form.

“That was the moment when it was a complete shock,” Dr.
Pruitt said.

A mutated gene can be put right by various mechanisms that
are already known, but all require a correct copy of the gene to be available to
serve as the template. The Purdue team scanned the DNA of the entire arabidopsis
genome for a second, cryptic copy of the hothead gene but could find none.

Dr. Pruitt and his colleagues argue that a correct template
must exist, but because it is not in the form of DNA, it probably exists as RNA,
DNA’s close chemical cousin. RNA performs many important roles in the cell, and
is the hereditary material of some viruses. But it is less stable than DNA, and
so has been regarded as unsuitable for preserving the genetic information of
higher organisms.

Dr. Pruitt said he favored the idea that there is an RNA
backup copy for the entire genome, not just the hothead gene, and that it might
be set in motion when the plant was under stress, as is the case with those
having mutated hothead genes.

He and other experts said it was possible that an entire
RNA backup copy of the genome could exist without being detected, especially
since there has been no reason until now to look for it.

Scientific journals often take months or years to get
comfortable with articles presenting novel ideas. But Nature accepted the paper
within six weeks of receiving it. Dr. Christopher Surridge, a biology editor at
Nature, said the finding had been discussed at scientific conferences for quite
a while, with people saying it was impossible and proposing alternative
explanations. But the authors had checked all these out and disposed of them,
Dr. Surridge said.

As for their proposal of a backup RNA genome, “that is very
much a hypothesis, and basically the least mad hypothesis for how this might be
working,” Dr. Surridge said.

Dr. Haig, the evolutionary biologist, said that the finding
was fascinating but that it was too early to try to interpret it. He noted that
if there was a cryptic template, it ought to be more resistant to mutation than
the DNA it helps correct. Yet it is hard to make this case for RNA, which
accumulates many more errors than DNA when it is copied by the cell.

He said that the mechanism, if confirmed, would be an
unprecedented exception to Mendel’s laws of inheritance, since the DNA sequence
itself is changed. Imprinting, an odd feature of inheritance of which Dr. Haig
is a leading student, involves inherited changes to the way certain genes are
activated, not to the genes themselves.

The finding poses a puzzle for evolutionary theory because
it corrects mutations, which evolution depends on as generators of novelty. Dr.
Meyerowitz said he did not see this posing any problem for evolution because it
seems to happen only rarely. “What keeps Darwinian evolution intact is that this
only happens when there is something wrong,” Dr. Surridge said.

The finding could undercut a leading theory of why sex is
necessary. Some biologists say sex is needed to discard the mutations, almost
all of them bad, that steadily accumulate on the genome. People inherit half of
their genes from each parent, which allows the half left on the cutting room
floor to carry away many bad mutations. Dr. Pruitt said the backup genome could
be particularly useful for self-fertilizing plants, as arabidopsis is, since it
could help avoid the adverse effects of inbreeding. It might also operate in the
curious organisms known as bdelloid rotifers that are renowned for not having
had sex for millions of years, an abstinence that would be expected to seriously
threaten their Darwinian fitness.

Dr. Pruitt said it was not yet known if other organisms
besides arabidopsis could possess the backup system. Colleagues had been quite
receptive to the idea because “biologists have gotten used to the unexpected,”
he said, referring to a spate of novel mechanisms that have recently come to
light, several involving RNA.

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March 26, 2005 at 9:48 AM