Archiver > GENEALOGY-DNA > 2005-03 > 1111636831

From: adam bradford <>
Subject: Cryptic Backup Copy of Genome - "Hothead Gene"
Date: Wed, 23 Mar 2005 23:00:31 -0500

Thought some of you might find this interesting.


New York Times - March 23, 2005
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

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

"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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