July 20, 2006 -- A newly cloned gene in corn will help explain how unusual interactions
between a parent's genes can have lasting effects in future
generations. The finding has implications for breeding better crop
plants and unraveling complex genetic diseases.
The
new research indicates that an additional molecule, DNA's little cousin
RNA, is needed for the intriguing gene interactions known as
paramutation. Paramutation doesn't follow the laws of classical
Mendelian genetics.
"Paramutation is this incredibly interesting, tantalizing violation of
Mendel's laws," said senior author Vicki L. Chandler, director of BIO5
Institute at The University of Arizona in Tucson. "It's been known to
exist for 50 years, but nobody understood the underlying mechanism."
Classical
genetics states that when offspring inherit genes from their parents,
the genes function in the children the same way the genes functioned in
the parent.
When paramutation occurs, one version of the
parent's gene orders the other to act differently in the next
generation. The gene functions differently in the offspring, even
though its DNA is identical to the parent's version.
It happens
even when the kids don't inherit the bossy version of the gene. The
phenomenon was originally found in corn and has since been found in
other organisms, including mammals.
"In previous work we
identified a gene that is absolutely required for paramutation to
happen," said Chandler, a UA Regents' Professor of plant sciences and
of molecular and cellular biology. "Now we've figured out what that
gene does, and it's exciting because it suggests a mechanism for how
this process works."
Chandler's work is the first to point out that an enzyme known as an RNA-dependent RNA polymerase is needed for paramutation.
Corn,
also known as maize, is the most economically important crop plant in
the United States. Better understanding of plant genetics will help
breeders develop improved strains of crops.
Understanding
paramutation and similar non-Mendelian genetic phenomena also has
implications for human health. For some human diseases, a genetic
component is known to exist but has been hard to decipher.
Non-Mendelian effects may be at work in those diseases.
"Gene
interactions in parents that change the way a gene functions in the
progeny are going to contribute to very unexpected inheritance patterns
that complicate identifying genes involved in human disease," said
Chandler, who holds the Carl E. and Patricia Weiler Endowed Chair for
Excellence in Agriculture and Life Sciences at UA.
Chandler and
her colleagues will publish their new findings in the July 20 issue of
the journal Nature. The article's title and a complete list of authors
and their affiliations is at the end of the release. The National
Science Foundation, the National Institutes of Health and the Howard
Hughes Medical Institute funded the research.
The Chandler lab
investigated a gene called b1 that controls whether a corn plant has a
purple or green stalk. A plant has two copies of each gene, one from
each parent.
One version, or allele, of the gene codes for a
purple pigment. Generally, plants need just one copy of that allele,
known as B-Intense or B-I, to be the color purple.
But whether a
B-I-carrying plant is actually purple depends on the company B-I keeps.
If the plant's other b1 allele is the "paramutagenic" B' variety, the
B-I allele is silenced. The resulting plant is mostly green.
And
although B-I's DNA doesn't change, in subsequent generations the
silenced B-I allele behaves as if it had mutated - the B-I-carrying
progeny are mostly green, rather than being deep purple.
"It
cannot revert - it's a one-way street," said co-author Lyudmila
Sidorenko, an assistant research scientist in Chandler's lab.
Chandler
and her colleagues wanted to know how the B' allele changed B-I's
behavior without actually changing B-I's DNA. They already knew that
paramutation required normal versions of the mediator of paramutation 1
(mop1) gene.
Plants with normal mop1 genes and one B-I allele and one B' allele turned out as expected - mostly green.
However,
B-I/B' plants with two mutant mop1 genes were deep purple - they looked
as if the purple-suppressing B' allele wasn't present. This
demonstrated that normal mop1 was necessary for the B' allele to
silence B-I.
The scientists mapped mop1's location on one of the
corn's chromosomes and cloned the gene. The mop1 gene makes an enzyme
called RNA-dependent RNA polymerase (RDRP). Mutant mop1 genes can't
produce the enzyme.
The team had previously suspected a role for
RNA, best known for mediating the transfer of information from DNA to a
cell's protein-making machinery. This new result provides strong
evidence that RNA is indeed involved.
The researchers
hypothesize that mop1 amplifies the RNA signals coming from a key
region of the B-I and B' allele. That key region is a particular DNA
sequence that is repeated seven times.
The researchers hypothesize that those many RNA molecules silence the B-I and B' alleles.
Chandler said, "It's exciting because it's a new role for RNA."
The
researchers' next step is figuring out exactly how RNA suppresses the
function of the b1 gene and how those cease-and-desist orders are
faithfully transmitted to progeny in the absence of changes in the DNA.
Source : University of Arizona
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